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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators

Author(s): Khandan Ilkhani, Milad Bastami, Soheila Delgir, Asma Safi, Shahrzad Talebian and Mohammad-Reza Alivand*

Volume 21, Issue 2, 2021

Published on: 10 September, 2020

Page: [254 - 266] Pages: 13

DOI: 10.2174/1871520620666200910123428

Price: $65

Abstract

Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.

Keywords: Neoplasm metabolism, exosomes, hypoxia, cancer-associated fibroblasts, tumor microenvironment, CAF-derived exosomes.

Graphical Abstract

[1]
Luo, X.; Zhao, X.; Cheng, C.; Li, N.; Liu, Y.; Cao, Y. The implications of signaling lipids in cancer metastasis. Exp. Mol. Med., 2018, 50(9), 127.
[http://dx.doi.org/10.1038/s12276-018-0150-x] [PMID: 30242145]
[2]
Heiden, M.G. Vander, Understanding the Warburg Effect: The metabolic requirements of cell proliferation. Science, 2009, 324(5930), 1029-1033.
[3]
Dvorak, H.F.; Weaver, V.M.; Tlsty, T.D.; Bergers, G. Tumor microenvironment and progression. J. Surg. Oncol., 2011, 103(6), 468-474.
[http://dx.doi.org/10.1002/jso.21709] [PMID: 21480238]
[4]
Schwartz, L.; Seyfried, T.; Alfarouk, K.O.; Da Veiga Moreira, J.; Fais, S. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH. Semin. Cancer Biol., 2017, 43, 134-138.
[http://dx.doi.org/10.1016/j.semcancer.2017.01.005] [PMID: 28122260]
[5]
Moreira, J.D.; Hamraz, M.; Abolhassani, M.; Bigan, E.; Pérès, S.; Paulevé, L.; Nogueira, M.L.; Steyaert, J.M.; Schwartz, L. The redox status of cancer cells supports mechanisms behind the Warburg effect. Metabolites, 2016, 6(4), 1-12.
[http://dx.doi.org/10.3390/metabo6040033] [PMID: 27706102]
[6]
Joyce, J.A.; Pollard, J.W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer, 2009, 9(4), 239-252.
[http://dx.doi.org/10.1038/nrc2618] [PMID: 19279573]
[7]
Tomasetti, M.; Lee, W.; Santarelli, L.; Neuzil, J. Exosome-derived microRNAs in cancer metabolism: Possible implications in cancer diagnostics and therapy. Expr. Mulecular Med., 2017, 49(1), e285-e311.
[http://dx.doi.org/10.1038/emm.2016.153]
[8]
Fiaschi, T.; Marini, A.; Giannoni, E.; Taddei, M.L.; Gandellini, P.; De Donatis, A.; Lanciotti, M.; Serni, S.; Cirri, P.; Chiarugi, P. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res., 2012, 72(19), 5130-5140.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1949] [PMID: 22850421]
[9]
Wang, M.; Zhao, J.; Zhang, L.; Wei, F.; Lian, Y.; Wu, Y. Role of tumor microenvironment in tumorigenesis. J. CA., 2017, 8(5), 761-773.
[10]
Kosaka, N.; Yoshioka, Y.; Fujita, Y.; Ochiya, T. Versatile roles of extracellular vesicles in cancer. J. Clin. Invest., 2016, 126(4), 1163-1172.
[http://dx.doi.org/10.1172/JCI81130] [PMID: 26974161]
[11]
Pavlides, S.; Whitaker-Menezes, D.; Castello-Cros, R.; Flomenberg, N.; Witkiewicz, A.K.; Frank, P.G.; Casimiro, M.C.; Wang, C.; Fortina, P.; Addya, S.; Pestell, R.G.; Martinez-Outschoorn, U.E.; Sotgia, F.; Lisanti, M.P. The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle, 2009, 8(23), 3984-4001.
[http://dx.doi.org/10.4161/cc.8.23.10238] [PMID: 19923890]
[12]
Mole, D.R.; Blancher, C.; Copley, R.R.; Pollard, P.J.; Gleadle, J.M.; Ragoussis, J.; Ratcliffe, P.J. Genome-wide association of Hypoxia-Inducible Factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J. Biol. Chem., 2009, 284(25), 16767-16775.
[http://dx.doi.org/10.1074/jbc.M901790200] [PMID: 19386601]
[13]
Wang, G.L.; Jiang, B.H.; Rue, E.A.; Semenza, G.L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. USA, 1995, 92(12), 5510-5514.
[http://dx.doi.org/10.1073/pnas.92.12.5510] [PMID: 7539918]
[14]
Martinez-outschoorn, U.E.; Trimmer, C.; Lin, Z. Autophagy in cancer associated fibroblasts promotes tumor cell survival Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment. Cell Cycle, 2010, 4101(9), 17.
[15]
McNeill, L.A.; Hewitson, K.S.; Claridge, T.D.; Seibel, J.F.; Horsfall, L.E.; Schofield, C.J. Hypoxia-inducible Factor Asparaginyl Hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803. Biochem. J., 2002, 367(Pt 3), 571-575.
[http://dx.doi.org/10.1042/bj20021162] [PMID: 12215170]
[16]
DeBerardinis, R.J.; Lum, J.J.; Hatzivassiliou, G.; Thompson, C.B. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab., 2008, 7(1), 11-20.
[http://dx.doi.org/10.1016/j.cmet.2007.10.002] [PMID: 18177721]
[17]
DeBerardinis, R.J.; Mancuso, A.; Daikhin, E.; Nissim, I.; Yudkoff, M.; Wehrli, S.; Thompson, C.B. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. USA, 2007, 104(49), 19345-19350.
[http://dx.doi.org/10.1073/pnas.0709747104] [PMID: 18032601]
[18]
Gordan, J.D.; Thompson, C.B.; Simon, M.C. HIF and c-Myc: Sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell, 2007, 12(2), 108-113.
[http://dx.doi.org/10.1016/j.ccr.2007.07.006] [PMID: 17692803]
[19]
Li, C.; Zhang, G.; Zhao, L.; Ma, Z.; Chen, H. Metabolic reprogramming in cancer cells: Glycolysis, glutaminolysis, and Bcl-2 proteins as novel therapeutic targets for cancer. World J. Surg. Oncol., 2016, 14(1), 15.
[http://dx.doi.org/10.1186/s12957-016-0769-9] [PMID: 26791262]
[20]
Zhang, J.; Fan, J.; Venneti, S.; Cross, J.R.; Takagi, T.; Bhinder, B.; Djaballah, H.; Kanai, M.; Cheng, E.H.; Judkins, A.R.; Pawel, B.; Baggs, J.; Cherry, S.; Rabinowitz, J.D.; Thompson, C.B. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol. Cell, 2014, 56(2), 205-218.
[http://dx.doi.org/10.1016/j.molcel.2014.08.018] [PMID: 25242145]
[21]
Li, H.; Zhou, F.; Du, W.; Dou, J.; Xu, Y.; Gao, W.; Chen, G.; Zuo, X.; Sun, L.; Zhang, X.; Yang, S. Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells. Biotechnol. Appl. Biochem., 2016, 63(3), 328-333.
[http://dx.doi.org/10.1002/bab.1383] [PMID: 25858017]
[22]
Kalluri, R.; Neilson, E.G. Epithelial-mesenchymal transition and its implications for fibrosis. J. Clin. Invest., 2003, 112(12), 1776-1784.
[http://dx.doi.org/10.1172/JCI200320530] [PMID: 14679171]
[23]
Syn, N.; Wang, L.; Sethi, G.; Thiery, J-P.; Goh, B-C. Exosome-mediated metastasis: From epithelial-mesenchymal transition to escape from immunosurveillance. Trends Pharmacol. Sci., 2016, 37(7), 606-617.
[http://dx.doi.org/10.1016/j.tips.2016.04.006] [PMID: 27157716]
[24]
Kalluri, R.; Weinberg, R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest., 2009, 119(6), 1420-1428.
[http://dx.doi.org/10.1172/JCI39104] [PMID: 19487818]
[25]
Fidler, S.J. The pathogenesis of cancer metastasis: The “seed and soil” hypothesis revisited. Nature, 2003, 3(6), 453-458.
[http://dx.doi.org/10.1038/nrc1098]
[26]
Najafi, M.; Goradel, N.H.; Farhood, B.; Salehi, E.; Solhjoo, S.; Toolee, H.; Kharazinejad, E.; Mortezaee, K. Tumor microenvironment: Interactions and therapy. J. Cell. Physiol., 2019, 234(5), 5700-5721.
[http://dx.doi.org/10.1002/jcp.27425] [PMID: 30378106]
[27]
Mueller, M.M.; Norbert, E. Fusenig. Friends or foes - bipolar effects of the tumour stroma in cancer. Nature, 2004, 4(11), 839-849.
[28]
Corrales, L.; Matson, V.; Flood, B.; Spranger, S.; Gajewski, T.F. Innate immune signaling and regulation in cancer immunotherapy. Cell Res., 2017, 27(1), 96-108.
[http://dx.doi.org/10.1038/cr.2016.149] [PMID: 27981969]
[29]
Ghesquière, B.; Wong, B.W.; Kuchnio, A.; Carmeliet, P. Metabolism of stromal and immune cells in health and disease. Nature, 2014, 511(7508), 167-176.
[http://dx.doi.org/10.1038/nature13312] [PMID: 25008522]
[30]
Netea-Maier, R.T.; Smit, J.W.A.; Netea, M.G. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship. Cancer Lett., 2018, 413, 102-109.
[http://dx.doi.org/10.1016/j.canlet.2017.10.037] [PMID: 29111350]
[31]
Xiang, T.; Long, H.; He, L.; Han, X.; Lin, K.; Liang, Z.; Zhuo, W.; Xie, R.; Zhu, B. Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer. Oncogene, 2015, 34(2), 165-176.
[http://dx.doi.org/10.1038/onc.2013.537] [PMID: 24362529]
[32]
Zecchin, A.; Kalucka, J.; Dubois, C.; Carmeliet, P. How endothelial cells adapt their metabolism to form vessels in tumors. Front. Immunol., 2017, 8, 1750.
[http://dx.doi.org/10.3389/fimmu.2017.01750] [PMID: 29321777]
[33]
Yang, J.D.; Nakamura, I.; Roberts, L.R. The tumor microenvironment in hepatocellular carcinoma: Current status and therapeutic targets. Semin. Cancer Biol., 2011, 21(1), 35-43.
[http://dx.doi.org/10.1016/j.semcancer.2010.10.007] [PMID: 20946957]
[34]
Castiello, L.; Sestili, P.; Schiavoni, G.; Dattilo, R.; Monque, D.M.; Ciaffoni, F.; Iezzi, M.; Lamolinara, A.; Sistigu, A.; Moschella, F.; Pacca, A.M.; Macchia, D.; Ferrantini, M.; Zeuner, A.; Biffoni, M.; Proietti, E.; Belardelli, F.; Aricò, E. Disruption of IFN-I signaling promotes HER2/neu tumor progression and breast cancer stem cells. cancer. Cancer Immunol. Res., 2018, 6(6), 658-670.
[http://dx.doi.org/10.1158/2326-6066.CIR-17-0675] [PMID: 29622580]
[35]
Doherty, M.R.; Cheon, H.; Junk, D.J.; Vinayak, S.; Varadan, V.; Telli, M.L.; Ford, J.M.; Stark, G.R.; Jackson, M.W. Interferon-beta represses cancer stem cell properties in triple-negative breast cancer. Proc. Natl. Acad. Sci. USA, 2017, 114(52), 13792-13797.
[http://dx.doi.org/10.1073/pnas.1713728114] [PMID: 29229854]
[36]
Pitroda, S.P.; Wakim, B.T.; Sood, R.F.; Beveridge, M.G.; Beckett, M.A.; MacDermed, D.M.; Weichselbaum, R.R.; Khodarev, N.N. STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect. BMC Med., 2009, 7(1), 68.
[http://dx.doi.org/10.1186/1741-7015-7-68] [PMID: 19891767]
[37]
Dong, Y.; Zhang, Y.; Kang, W.; Wang, G.; Chen, H.; Higashimori, A. VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6. Theranostics, 2019, 9(22), 6517-6531.
[http://dx.doi.org/10.7150/thno.34989]
[38]
Vallée, A.; Lecarpentier, Y.; Guillevin, R.; Vallée, J-N. Aerobic glycolysis hypothesis through WNT/Beta-Catenin pathway in exudative age-related macular degeneration. J. Mol. Neurosci., 2017, 62(3-4), 368-379.
[http://dx.doi.org/10.1007/s12031-017-0947-4] [PMID: 28689265]
[39]
Otegbeye, F.; Ojo, E.; Moreton, S.; Mackowski, N.; Lee, D.A.; de Lima, M.; Wald, D.N. Inhibiting TGF-beta signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models. PLoS One, 2018, 13(1)e0191358
[http://dx.doi.org/10.1371/journal.pone.0191358] [PMID: 29342200]
[40]
Richards, K.E.; Zeleniak, A.E.; Fishel, M.L.; Wu, J.; Littlepage, L.E.; Hill, R. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene, 2017, 36(13), 1770-1778.
[http://dx.doi.org/10.1038/onc.2016.353] [PMID: 27669441]
[41]
Pantuck, A.J.; An, J.; Liu, H.; Rettig, M.B. NF-kappaB-dependent plasticity of the epithelial to mesenchymal transition induced by Von Hippel-Lindau inactivation in renal cell carcinomas. Cancer Res., 2010, 70(2), 752-761.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2211] [PMID: 20068166]
[42]
Min, C.; Eddy, S.F.; Sherr, D.H.; Sonenshein, G.E. NF-kappaB and epithelial to mesenchymal transition of cancer. J. Cell. Biochem., 2008, 104(3), 733-744.
[http://dx.doi.org/10.1002/jcb.21695] [PMID: 18253935]
[43]
Li, T.L.A. Glutamine metabolism in cancer. Exp. Med. Biol., 2018, 1063, 13-32.
[http://dx.doi.org/10.1007/978-3-319-77736-8_2]
[44]
Ye, H.; Zhou, Q.; Zheng, S.; Li, G.; Lin, Q.; Wei, L.; Fu, Z.; Zhang, B.; Liu, Y.; Li, Z.; Chen, R. Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma. Cell Death Dis., 2018, 9(5), 453.
[http://dx.doi.org/10.1038/s41419-018-0486-0] [PMID: 29670110]
[45]
Fessler, E.; Borovski, T.; Medema, J.P. Endothelial cells induce cancer stem cell features in differentiated glioblastoma cells via bFGF. Mol. Cancer, 2015, 14(1), 157.
[http://dx.doi.org/10.1186/s12943-015-0420-3] [PMID: 26282129]
[46]
Kumari, N.; Dwarakanath, B.S.; Das, A.; Bhatt, A.N. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol., 2016, 37(9), 11553-11572.
[http://dx.doi.org/10.1007/s13277-016-5098-7] [PMID: 27260630]
[47]
Mantovani, A.; Germano, G.; Marchesi, F.; Locatelli, M.; Biswas, S.K. Cancer-promoting tumor-associated macrophages: new vistas and open questions. Eur. J. Immunol., 2011, 41(9), 2522-2525.
[http://dx.doi.org/10.1002/eji.201141894] [PMID: 21952810]
[48]
Ghandadi, M.; Sahebkar, A. Interleukin-6: A critical cytokine in cancer multidrug resistance. Curr. Pharm. Des., 2016, 22(5), 518-526.
[http://dx.doi.org/10.2174/1381612822666151124234417] [PMID: 26601970]
[49]
Skolekova, S.; Matuskova, M.; Bohac, M.; Toro, L.; Durinikova, E.; Tyciakova, S.; Demkova, L.; Gursky, J.; Kucerova, L. Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells. Cell Commun. Signal., 2016, 14(1), 4.
[http://dx.doi.org/10.1186/s12964-016-0127-0] [PMID: 26759169]
[50]
Abiko, K.; Matsumura, N.; Hamanishi, J.; Horikawa, N.; Murakami, R.; Yamaguchi, K.; Yoshioka, Y.; Baba, T.; Konishi, I.; Mandai, M. IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br. J. Cancer, 2015, 112(9), 1501-1509.
[http://dx.doi.org/10.1038/bjc.2015.101] [PMID: 25867264]
[51]
Mary, R. Interferon-beta represses cancer stem cell properties in triple-negative breast cancer. Proceed. Natl. Acad. Sci. U.S.A, 2017, 144(52), 13792-13797.
[52]
Shen, J.; Xiao, Z.; Zhao, Q.; Li, M.; Wu, X.; Zhang, L. Anti-cancer therapy with TNF α and IFN γ : A comprehensive review. Cell Prolif., 2018, 51(4)e12441
[53]
Böttcher, J.P.; Bonavita, E.; Chakravarty, P.; Blees, H.; Cabeza-Cabrerizo, M.; Sammicheli, S.; Rogers, N.C.; Sahai, E.; Zelenay, S.; Reis, E. Sousa, C. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell, 2018, 172(5), 1022-1037.
[http://dx.doi.org/10.1016/j.cell.2018.01.004] [PMID: 29429633]
[54]
Pathria, P.; Louis, T.L.; Varner, J.A. Targeting tumor-associated macrophages in cancer. Trends Immunol., 2019, 40(4), 310-327.
[http://dx.doi.org/10.1016/j.it.2019.02.003] [PMID: 30890304]
[55]
Xing, F.; Saidou, J.; Watabe, K. Cancer Associated Fibroblasts (CAFs) in tumor microenvironment. Front. Biosci., 2011, 1(15), 166-179.
[56]
Donnarumma, E.; Fiore, D.; Nappa, M.; Roscigno, G.; Adamo, A.; Iaboni, M.; Russo, V.; Affinito, A.; Puoti, I.; Quintavalle, C.; Rienzo, A.; Piscuoglio, S.; Thomas, R.; Condorelli, G. Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer. Oncotarget, 2017, 8(12), 19592-19608.
[http://dx.doi.org/10.18632/oncotarget.14752] [PMID: 28121625]
[57]
Cirri, P.; Chiarugi, P. Cancer-associated-fibroblasts and tumour cells: A diabolic liaison driving cancer progression. Cancer Metastasis Rev., 2012, 31(1-2), 195-208.
[58]
Giannoni, E.; Bianchini, F.; Masieri, L.; Serni, S.; Torre, E. Reciprocal activation of prostate cancer cells and cancer- associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness Am. Assoc. Cancer Res., 2010, 6945-6957.
[59]
Bist, A.; Fielding, C.J.; Fielding, P.E. p53 regulates caveolin gene transcription, cell cholesterol, and growth by a novel mechanism. Biochemistry, 2000, 39(8), 1966-1972.
[http://dx.doi.org/10.1021/bi991721h] [PMID: 10684646]
[60]
Yamao, T.; Yamashita, Y.I.; Yamamura, K.; Nakao, Y.; Tsukamoto, M.; Nakagawa, S.; Okabe, H.; Hayashi, H.; Imai, K.; Baba, H. Cellular senescence, represented by expression of Caveolin-1, in cancer-associated fibroblasts promotes tumor invasion in pancreatic cancer. Ann. Surg. Oncol., 2019, 26(5), 1552-1559.
[http://dx.doi.org/10.1245/s10434-019-07266-2] [PMID: 30805811]
[61]
Bonuccelli, G.; Whitaker-Menezes, D.; Castello-Cros, R.; Pavlides, S.; Pestell, R.G.; Fatatis, A.; Witkiewicz, A.K.; Vander Heiden, M.G.; Migneco, G.; Chiavarina, B.; Frank, P.G.; Capozza, F.; Flomenberg, N.; Martinez-Outschoorn, U.E.; Sotgia, F.; Lisanti, M.P. The reverse Warburg effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle, 2010, 9(10), 1960-1971.
[http://dx.doi.org/10.4161/cc.9.10.11601] [PMID: 20495363]
[62]
Martinez-Outschoorn, U.E.; Lisanti, M.P.; Sotgia, F. Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth. Semin. Cancer Biol., 2014, 25, 47-60.
[http://dx.doi.org/10.1016/j.semcancer.2014.01.005] [PMID: 24486645]
[63]
Pavlides, S.; Tsirigos, A.; Migneco, G.; Whitaker-Menezes, D.; Chiavarina, B.; Flomenberg, N.; Frank, P.G.; Casimiro, M.C.; Wang, C.; Pestell, R.G.; Martinez-Outschoorn, U.E.; Howell, A.; Sotgia, F.; Lisanti, M.P. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle, 2010, 9(17), 3485-3505.
[http://dx.doi.org/10.4161/cc.9.17.12721] [PMID: 20861672]
[64]
Brown, G.C. Nitric oxide and mitochondrial respiration. Biochim Biophys acta (BBA)-. Bioenergetics, 1999, 1411(2-3), 351-369.
[http://dx.doi.org/10.1016/S0005-2728(99)00025-0]
[65]
Xiong, S.; Wang, R.; Chen, Q.; Luo, J.; Wang, J.; Zhao, Z.; Li, Y.; Wang, Y.; Wang, X.; Cheng, B. Cancer-associated fibroblasts promote stem cell-like properties of hepatocellular carcinoma cells through IL-6/STAT3/Notch signaling. Am. J. Cancer Res., 2018, 8(2), 302-316.
[PMID: 29511600]
[66]
Jahangiri, B.; Khalaj-Kondori, M.; Asadollahi, E.; Sadeghizadeh, M. Cancer-associated fibroblasts enhance cell proliferation and metastasis of colorectal cancer SW480 cells by provoking long noncoding RNA UCA1. J. Cell Commun. Signal., 2019, 13(1), 53-64.
[http://dx.doi.org/10.1007/s12079-018-0471-5] [PMID: 29948578]
[67]
Zhuang, J.; Lu, Q.; Shen, B.; Huang, X.; Shen, L.; Zheng, X.; Huang, R.; Yan, J.; Guo, H. TGFβ1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Sci. Rep., 2015, 5, 11924.
[http://dx.doi.org/10.1038/srep11924] [PMID: 26152796]
[68]
Lakins, M.A.; Ghorani, E.; Munir, H.; Martins, C.P.; Shields, J.D. Cancer-associated fibroblasts induce antigen-specific deletion of CD8 + T Cells to protect tumour cells. Nat. Commun., 2018, 9(1), 948.
[http://dx.doi.org/10.1038/s41467-018-03347-0] [PMID: 29507342]
[69]
Au Yeung, C.L.; Co, N.N.; Tsuruga, T.; Yeung, T.L.; Kwan, S.Y.; Leung, C.S.; Li, Y.; Lu, E.S.; Kwan, K.; Wong, K.K.; Schmandt, R.; Lu, K.H.; Mok, S.C. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat. Commun., 2016, 7, 11150.
[http://dx.doi.org/10.1038/ncomms11150] [PMID: 27021436]
[70]
Shintani, Y.; Fujiwara, A.; Kimura, T.; Kawamura, T.; Funaki, S.; Minami, M.; Okumura, M. IL-6 secreted from cancer-associated fibroblasts mediates chemoresistance in NSCLC by increasing epithelial-mesenchymal transition signaling. J. Thorac. Oncol., 2016, 11(9), 1482-1492.
[http://dx.doi.org/10.1016/j.jtho.2016.05.025] [PMID: 27287412]
[71]
Wen, S.; Hou, Y.; Fu, L.; Xi, L.; Yang, D.; Zhao, M.; Qin, Y.; Sun, K.; Teng, Y.; Liu, M. Cancer-Associated Fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin β3-p38 MAPK signalling. Cancer Lett., 2019, 442, 320-332.
[http://dx.doi.org/10.1016/j.canlet.2018.10.015] [PMID: 30391782]
[72]
Fu, Y.; Liu, S.; Yin, S.; Niu, W.; Xiong, W.; Tan, M.; Li, G.; Zhou, M. The reverse Warburg effect is likely to be an Achilles’ heel of cancer that can be exploited for cancer therapy. Oncotarget, 2017, 8(34), 57813-57825.
[http://dx.doi.org/10.18632/oncotarget.18175] [PMID: 28915713]
[73]
Fiaschi, T.; Marini, A.; Giannoni, E.; Taddei, M.L.; Gandellini, P.; De, A. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res., 2012, 72(14), 5130-5141.
[74]
Yan, W.; Wu, X.; Zhou, W.; Fong, M.Y.; Cao, M.; Liu, J.; Liu, X.; Chen, C.H.; Fadare, O.; Pizzo, D.P.; Wu, J.; Liu, L.; Liu, X.; Chin, A.R.; Ren, X.; Chen, Y.; Locasale, J.W.; Wang, S.E. Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nat. Cell Biol., 2018, 20(5), 597-609.
[http://dx.doi.org/10.1038/s41556-018-0083-6] [PMID: 29662176]
[75]
Choi, J.; Kim, D.H.; Jung, W.H.; Koo, J.S. Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype. Breast Cancer Res., 2013, 15(5), R78.
[http://dx.doi.org/10.1186/bcr3472] [PMID: 24020991]
[76]
Zheng, J. Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation. (Review). Oncol. Lett., 2012, 4(6), 1151-1157.
[http://dx.doi.org/10.3892/ol.2012.928] [PMID: 23226794]
[77]
Zhao, H.; Yang, L.; Baddour, J.; Achreja, A.; Bernard, V.; Moss, T.; Marini, J.C.; Tudawe, T.; Seviour, E.G.; San Lucas, F.A.; Alvarez, H.; Gupta, S.; Maiti, S.N.; Cooper, L.; Peehl, D.; Ram, P.T.; Maitra, A.; Nagrath, D. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. eLife, 2016, 5e10250
[http://dx.doi.org/10.7554/eLife.10250] [PMID: 26920219]
[78]
Zhang, D.; Wang, Y.; Shi, Z.; Liu, J.; Sun, P.; Hou, X.; Zhang, J.; Zhao, S.; Zhou, B.P.; Mi, J. Metabolic reprogramming of cancer-associated fibroblasts by IDH3α downregulation. Cell Rep., 2015, 10(8), 1335-1348.
[http://dx.doi.org/10.1016/j.celrep.2015.02.006] [PMID: 25732824]
[79]
Koukourakis, M.I.; Giatromanolaki, A.; Harris, A.L.; Sivridis, E.; Giatromanolaki, A.; Harris, A.L. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res., 2006, 66(2), 632-637.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3260] [PMID: 16423989]
[80]
Lazar, I.; Clement, E.; Dauvillier, S.; Milhas, D.; Ducoux-Petit, M.; LeGonidec, S.; Moro, C.; Soldan, V.; Dalle, S.; Balor, S.; Golzio, M.; Burlet-Schiltz, O.; Valet, P.; Muller, C.; Nieto, L. Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: A novel mechanism linking obesity and cancer. Cancer Res., 2016, 76(14), 4051-4057.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0651] [PMID: 27216185]
[81]
Cho, J.A.; Park, H.; Lim, E.H.; Lee, K.W. Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int. J. Oncol., 2012, 40(1), 130-138.
[PMID: 21904773]
[82]
Johnsen, K.B.; Gudbergsson, J.M.; Skov, M.N.; Pilgaard, L.; Moos, T.; Duroux, M. A comprehensive overview of exosomes as drug delivery vehicles - Endogenous nanocarriers for targeted cancer therapy. BBA – Rev. Cancer, 2014, 1846(1), 75-87.
[83]
Bhagirath, D.; Yang, T.L.; Bucay, N.; Sekhon, K.; Majid, S.; Shahryari, V.; Dahiya, R.; Tanaka, Y.; Saini, S. microRNA-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res., 2018, 78(7), 1833-1844.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2069] [PMID: 29437039]
[84]
Wang, N.; Wang, L.; Yang, Y.; Gong, L.; Xiao, B.; Liu, X. A serum exosomal microRNA panel as a potential biomarker test for gastric cancer. Biochem. Biophys. Res. Commun., 2017, 493(3), 1322-1328.
[http://dx.doi.org/10.1016/j.bbrc.2017.10.003] [PMID: 28986250]
[85]
Rodríguez, M.; Bajo-Santos, C.; Hessvik, N.P.; Lorenz, S.; Fromm, B.; Berge, V.; Sandvig, K.; Linē, A.; Llorente, A. Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes. Mol. Cancer, 2017, 16(1), 156.
[http://dx.doi.org/10.1186/s12943-017-0726-4] [PMID: 28982366]
[86]
Zhang, W.; Ni, M.; Su, Y.; Wang, H.; Zhu, S.; Zhao, A.; Li, G. MicroRNAs in serum exosomes as potential biomarkers in clear-cell renal cell carcinoma. Eur. Urol. Focus, 2018, 4(3), 412-419.
[http://dx.doi.org/10.1016/j.euf.2016.09.007] [PMID: 28753793]
[87]
Matsumura, T.; Sugimachi, K.; Iinuma, H.; Takahashi, Y.; Kurashige, J.; Sawada, G.; Ueda, M.; Uchi, R.; Ueo, H.; Takano, Y.; Shinden, Y.; Eguchi, H.; Yamamoto, H.; Doki, Y.; Mori, M.; Ochiya, T.; Mimori, K. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br. J. Cancer, 2015, 113(2), 275-281.
[http://dx.doi.org/10.1038/bjc.2015.201] [PMID: 26057451]
[88]
Jin, X.; Chen, Y.; Chen, H.; Fei, S.; Chen, D.; Cai, X.; Liu, L.; Lin, B.; Su, H.; Zhao, L.; Su, M.; Pan, H.; Shen, L.; Xie, D.; Xie, C. Evaluation of tumor-derived exosomal miRNA as potential diagnostic biomarkers for early-stage non-small cell lung cancer using next-generation sequencing. Clin. Cancer Res., 2017, 23(17), 5311-5319.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0577] [PMID: 28606918]
[89]
Liu, Q.; Yu, Z.; Yuan, S.; Xie, W.; Li, C.; Hu, Z.; Xiang, Y.; Wu, N.; Wu, L.; Bai, L.; Li, Y. Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer. Oncotarget, 2017, 8(8), 13048-13058.
[http://dx.doi.org/10.18632/oncotarget.14369] [PMID: 28055956]
[90]
Tsukamoto, M.; Iinuma, H.; Yagi, T.; Matsuda, K.; Hashiguchi, Y. Circulating exosomal MicroRNA-21 as a biomarker in each tumor stage of colorectal cancer. Oncology, 2017, 92(6), 360-370.
[http://dx.doi.org/10.1159/000463387] [PMID: 28376502]
[91]
Erbes, T.; Hirschfeld, M.; Rücker, G.; Jaeger, M.; Boas, J.; Iborra, S.; Mayer, S.; Gitsch, G.; Stickeler, E. Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker. BMC Cancer, 2015, 15(1), 193.
[http://dx.doi.org/10.1186/s12885-015-1190-4] [PMID: 25886191]
[92]
Ge, R.; Tan, E.; Sharghi-Namini, S.; Asada, H.H. Exosomes in cancer microenvironment and beyond: Have we overlooked these extracellular messengers? Cancer Microenviron., 2012, 5(3), 323-332.
[http://dx.doi.org/10.1007/s12307-012-0110-2] [PMID: 22585423]
[93]
Fan, G-C. Hypoxic exosomes promote angiogenesis. Blood, 2014, 124(25), 3669-3670.
[http://dx.doi.org/10.1182/blood-2014-10-607846] [PMID: 25498451]
[94]
Matsuura, Y.; Wada, H.; Eguchi, H.; Gotoh, K.; Kobayashi, S.; Kinoshita, M.; Kubo, M.; Hayashi, K.; Iwagami, Y.; Yamada, D.; Asaoka, T.; Noda, T.; Kawamoto, K.; Takeda, Y.; Tanemura, M.; Umeshita, K.; Doki, Y.; Mori, M. Exosomal miR-155 derived from hepatocellular carcinoma cells under hypoxia promotes angiogenesis in endothelial cells. Dig. Dis. Sci., 2019, 64(3), 792-802.
[http://dx.doi.org/10.1007/s10620-018-5380-1] [PMID: 30465177]
[95]
Hood, J.L. Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes. Med. Hypotheses, 2016, 94, 118-122.
[http://dx.doi.org/10.1016/j.mehy.2016.07.009] [PMID: 27515216]
[96]
King, H.W.; Michael, M.Z.; Gleadle, J.M. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer, 2012, 12(1), 421.
[http://dx.doi.org/10.1186/1471-2407-12-421] [PMID: 22998595]
[97]
Kucharzewska, P.; Christianson, H.C.; Welch, J.E.; Svensson, K.J.; Fredlund, E.; Ringnér, M.; Mörgelin, M.; Bourseau-Guilmain, E.; Bengzon, J.; Belting, M. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc. Natl. Acad. Sci. USA, 2013, 110(18), 7312-7317.
[http://dx.doi.org/10.1073/pnas.1220998110] [PMID: 23589885]
[98]
Al-nedawi, K.; Meehan, B.; Kerbel, R.S.; Allison, A.C.; Rak, J. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic. EGFR Pro, 2009, 106(10), 3794-3799.
[99]
Lee, J.K.; Park, S.R.; Jung, B.K.; Jeon, Y.K.; Lee, Y.S.; Kim, M.K.; Kim, Y.G.; Jang, J.Y.; Kim, C.W. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS One, 2013, 8(12)e84256
[http://dx.doi.org/10.1371/journal.pone.0084256] [PMID: 24391924]
[100]
Chen, Y.; Zhao, Y.; Chen, W.; Xie, L.; Zhao, Z-A.; Yang, J.; Chen, Y.; Lei, W.; Shen, Z. MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction. Stem Cell Res. Ther., 2017, 8(1), 268.
[http://dx.doi.org/10.1186/s13287-017-0722-z] [PMID: 29178928]

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