Abstract
Background: Cancer kills nearly 9,000,000 people worldwide, and its mortality was reported up to 28% in the past decade. Few available tumor markers have been known to help early stage diagnosis. In this study, Endocan was taken as a novel tumor marker, which has been found in many cancers related to cancer cell proliferation, neoangiogenesis, etc.
Methods: Studies on Endocan and its correlation with cancer were reviewed, and key points of meaningful studies on the structure, pathways and targeted agents of Endocan were drawn.
Results: Endocan leads to tumorigenesis and promotes tumor cells proliferation via HGF/SF signal transmission pathway, suppresses tumor cells apoptosis via NF-κB signaling pathway and promotes angiogenesis within tumors via VEGF and HIF pathway. Medicine suppressing the expression of Endocan could prevent tumorigenesis and even improve survival rate of mice with tumor significantly.
Conclusion: Endocan is capable of promoting prognosis of cancer patients. Moreover, Endocan is supposed to a potential target of tumor-targeted therapy.
Graphical Abstract
[1]
Sumei, Z.; Shaolong, C.; Xiang, W.; Yinliang, Q.; Qing, Z.; Yuan, W. Endocan reduces the malign grade of gastric cancer cells by regulating associated protein expression. Tumour Biol., 2016, 37(11), 14915-14921.
[2]
Zhao, W.; Sun, M.; Li, S.; Wang, Y.; Liu, J. Biological and clinical implications of endocan in gastric cancer. Tumour Biol., 2014, 35(10), 10043-10049.
[3]
Sun, W.; Zhang, L.; Cheng, X.; Wang, X.; Xing, X.; Du, H.; Ji, J. Detection of serum endothelial cell specific molecule 1 in gastric cancer patients and its clinical significance. Zhonghua Wei Chang Wai Ke Za Zhi, 2014, 17(1), 51-55.
[4]
Liu, N.; Zhang, L.H.; Du, H.; Hu, Y.; Zhang, G.G.; Wang, X.H.; Li, J.Y.; Ji, J.F. Overexpression of endothelial cell specific molecule-1 (ESM-1) in gastric cancer. Ann. Surg. Oncol., 2010, 17(10), 2628-2639.
[5]
H J. Serum level of endothelial cell-specific molecule-1 and prognosis of colorectal cancer. Genet. Mol. Res., 2015, 2, 12.
[6]
Ji, N.Y.; Kim, Y.H.; Jang, Y.J.; Kang, Y.H.; Lee, C.I.; Kim, J.W.; Yeom, Y.I.; Chun, H.K.; Choi, Y.H.; Kim, J.H.; Kim, J.W.; Lee, H.G.; Song, E.Y. Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer. Cancer Sci., 2010, 101(10), 2248-2253.
[7]
Ozaki, K.; Toshikuni, N.; George, J.; Minato, T.; Matsue, Y.; Arisawa, T.; Tsutsumi, M. Serum endocan as a novel prognostic biomarker in patients with hepatocellular carcinoma. J. Cancer, 2014, 5(3), 221-230.
[8]
Nault, J.C.; Guyot, E.; Laguillier, C.; Chevret, S.; Ganne-Carrie, N.; N’Kontchou, G.; Beaugrand, M.; Seror, O.; Trinchet, J.C.; Coelho, J.; Lasalle, P.; Charnaux, N.; Delehedde, M.; Sutton, A.; Nahon, P. Serum proteoglycans as prognostic biomarkers of hepatocellular carcinoma in patients with alcoholic cirrhosis. Cancer Epidemiol. Biomarkers Prev., 2013, 22(8), 1343-1352.
[9]
Ziol, M.; Sutton, A.; Calderaro, J.; Barget, N.; Aout, M.; Leroy, V.; Blanc, J.F.; Sturm, N.; Bioulac-Sage, P.; Nahon, P.; Nault, J.C.; Charnaux, N.; N’kontchou, G.; Trinchet, J.C.; Delehedde, M.; Seror, O.; Beaugrand, M.; Vicaut, E.; Ganne-Carrié, N. ESM-1 expression in stromal cells is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma. J. Hepatol., 2013, 59(6), 1264-1270.
[10]
BD G. Endocan expression and relationship with survival in human non-small cell lung cancer. Clin. Cancer Res., 2006, 15, 77.
[11]
Rennel, E.; Mellberg, S.; Dimberg, A.; Petersson, L.; Botling, J.; Ameur, A.; Westholm, J.O.; Komorowski, J.; Lassalle, P.; Cross, M.J.; Gerwins, P. Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer. Exp. Cell Res., 2007, 313(7), 1285-1294.
[12]
Kim, K.H.; Lee, H.H.; Yoon, Y.E.; Na, J.C.; Kim, S.Y.; Cho, Y.I.; Hong, S.J.; Han, W.K. Clinical validation of serum endocan (ESM-1) as a potential biomarker in patients with renal cell carcinoma. Oncotarget, 2017, 9(1), 662-667.
[13]
Roudnicky, F.; Poyet, C.; Wild, P.; Krampitz, S.; Negrini, F.; Huggenberger, R.; Rogler, A.; Stöhr, R.; Hartmann, A.; Provenzano, M.; Otto, V.I.; Detmar, M. Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A-induced angiogenesis. Cancer Res., 2013, 73(3), 1097-1106.
[14]
Arslan, B.; Onuk, Ö.; Hazar, İ.; Aydın, M.; Çilesiz, N.C.; Eroglu, A.; Nuhoglu, B. Prognostic value of endocan in prostate cancer: clinicopathologic association between serum endocan levels and biochemical recurrence after radical prostatectomy. Tumori, 2017, 103(2), 204-208.
[15]
Laloglu, E.; Kumtepe, Y.; Aksoy, H.; Topdagi Yilmaz, E.P. Serum endocan levels in endometrial and ovarian cancers. J. Clin. Lab. Anal., 2017, 31(5), 66-68.
[16]
El Behery, M.M.; Seksaka, M.A.; Ibrahiem, M.A.; Saleh, H.S.; El Alfy, Y. Clinicopathological correlation of endocan expression and survival in epithelial ovarian cancer. Arch. Gynecol. Obstet., 2013, 288(6), 1371-1376.
[17]
Sagara, A.; Igarashi, K.; Otsuka, M.; Kodama, A.; Yamashita, M.; Sugiura, R.; Karasawa, T.; Arakawa, K.; Narita, M.; Kuzumaki, N.; Narita, M.; Kato, Y. Endocan as a prognostic biomarker of triple-negative breast cancer. Breast Cancer Res. Treat., 2017, 161(2), 269-278.
[18]
Xing, Y.; Wang, Y.; Wang, S.; Wang, X.; Fan, D.; Zhou, D.; An, J. Human cytomegalovirus infection contributes to glioma disease progression via upregulating endocan expression. Transl. Res., 2016, 177, 113-126.
[19]
Atukeren, P.; Kunbaz, A.; Turk, O.; Kemerdere, R.; Ulu, M.O.; Turkmen Inanir, N.; Tanriverdi, T. Expressions of endocan in patients with meningiomas and gliomas. Dis. Markers, 2016, 20167157039
[20]
Maurage, C.A.; Adam, E.; Minéo, J.F.; Sarrazin, S.; Debunne, M.; Siminski, R.M.; Baroncini, M.; Lassalle, P.; Blond, S.; Delehedde, M. Endocan expression and localization in human glioblastomas. J. Neuropathol. Exp. Neurol., 2009, 68(6), 633-641.
[21]
Delehedde, M.; Devenyns, L.; Maurage, C.A.; Vivès, R.R. Endocan in Cancers: A Lesson from a Circulating Dermatan Sulfate Proteoglycan. Int. J. Cell Biol., 2013, 2013, 1-11.
[22]
Cornelius, A.; Cortet-Rudelli, C.; Assaker, R.; Kerdraon, O.; Gevaert, M.H.; Prévot, V.; Lassalle, P.; Trouillas, J.; Delehedde, M.; Maurage, C.A. Endothelial expression of endocan is strongly associated with tumor progression in pituitary adenoma. Brain Pathol., 2012, 22(6), 757-764.
[23]
Lin, L.Y.; Yeh, Y.C.; Chu, C.H.; Won, J.G.S.; Shyr, Y.M.; Chao, Y.; Li, C.P.; Wang, S.E.; Chen, M.H. Endocan expression is correlated with poor progression-free survival in patients with pancreatic neuroendocrine tumors. Medicine (Baltimore), 2017, 96(41)e8262
[24]
Cai, L.; Leng, Z.G.; Guo, Y.H.; Lin, S.J.; Wu, Z.R.; Su, Z.P.; Lu, J.L.; Wei, L.F.; Zhuge, Q.C.; Jin, K.; Wu, Z.B. Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas. Endocrine, 2016, 52(3), 641-651.
[25]
Yang, W-E.; Hsieh, M-J.; Lin, C-W.; Kuo, C-Y.; Yang, S-F.; Chuang, C-Y. Chen, Mu-Kuan. Plasma levels of endothelial cell-specific molecule-1 as a potential biomarker of oral cancer progression. Int. J. Med. Sci., 2017, 14(11), 1094-1100.
[26]
Yu, P.H.; Chou, S.F.; Chen, C.L.; Hung, H.; Lai, C.Y.; Yang, P.M.; Jeng, Y.M.; Liaw, S.F.; Kuo, H.H.; Hsu, H.C.; Chen, J.Y.; Wang, W.B. Upregulation of endocan by Epstein-Barr virus latent membrane protein 1 and its clinical significance in nasopharyngeal carcinoma. PLoS One, 2013, 8(12) e82254
[27]
Bender, O.; Gunduz, M.; Cigdem, S.; Hatipoglu, O.F.; Acar, M.; Kaya, M.; Grenman, R.; Gunduz, E.; Ugur, K.S. Functional analysis of ESM1 by siRNA knockdown in primary and metastatic head and neck cancer cells. J. Oral Pathol. Med., 2018, 47(1), 40-47.
[28]
Tsai, J.C.; Zhang, J.; Minami, T.; Voland, C.; Zhao, S.; Yi, X.; Lassalle, P.; Oettgen, P.; Aird, W.C. Cloning and characterization of the human lung endothelial-cell-specific molecule-1 promoter. J. Vasc. Res., 2002, 39(2), 148-159.
[29]
Béchard, D.; Gentina, T.; Delehedde, M.; Scherpereel, A.; Lyon, M.; Aumercier, M.; Vazeux, R.; Richet, C.; Degand, P.; Jude, B.; Janin, A.; Fernig, D.G.; Tonnel, A.B.; Lassalle, P. Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. J. Biol. Chem., 2001, 276(51), 48341-48349.
[30]
Scherpereel, A.; Gentina, T.; Grigoriu, B.; Sénéchal, S.; Janin, A.; Tsicopoulos, A.; Plénat, F.; Béchard, D.; Tonnel, A.B.; Lassalle, P. Overexpression of endocan induces tumor formation. Cancer Res., 2003, 63(18), 6084-6089.
[31]
Aitkenhead, M.; Wang, S.J.; Nakatsu, M.N.; Mestas, J.; Heard, C.; Hughes, C.C. Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: Induction of ESM-1, (beta)ig-h3, and NrCAM. Microvasc. Res., 2002, 63(2), 159-171.
[32]
Cox, L.A.E.; van Eijk, L.T.; Ramakers, B.P.; Dorresteijn, M.J.; Gerretsen, J.; Kox, M.; Pickkers, P. Inflammation-induced increases in plasma endocan levels are associated with endothelial dysfunction in humans in vivo. Shock, 2015, 43(4), 322-326.
[33]
Mihajlovic, D.M.; Lendak, D.F.; Brkic, S.V.; Draskovic, B.G.; Mitic, G.P.; Novakov Mikic, A.S.; Cebovic, T.N. Endocan is useful biomarker of survival and severity in sepsis. Microvasc. Res., 2014, 93, 92-97.
[34]
Kirkpatrick, C.J.; Wagner, M.; Hermanns, I.; Klein, C.L.; Köhler, H.; Otto, M.; van Kooten, T.G.; Bittinger, F. Physiology and cell biology of the endothelium: A dynamic interface for cell communication. Int. J. Microcirc. Clin. Exp., 1997, 17(5), 231-240.
[35]
Hsiao, S.Y.; Kung, C.T.; Tsai, N.W.; Su, C.M.; Huang, C.C.; Lai, Y.R.; Wang, H.C.; Cheng, B.C.; Su, Y.J.; Lin, W.C.; Chiang, Y.F.; Lu, C.H. Concentration and value of endocan on outcome in adult patients after severe sepsis. Clin. Chim. Acta, 2018, 483, 275-280.
[36]
Rebollo, J.; Geliebter, J.; Reyes, N. ESM-1 siRNA knockdown decreased migration and expression of CXCL3 in prostate cancer cells. Int. J. Biomed. Sci., 2017, 13(1), 35-42.
[37]
Schallner, N.; Ulbrich, F.; Engelstaedter, H.; Biermann, J.; Auwaerter, V.; Loop, T.; Goebel, U. Isoflurane but not sevoflurane or desflurane aggravates injury to neurons in vitro and in vivo via p75NTR-NF-ĸB activation. Anesth. Analg., 2014, 119(6), 1429-1441.
[38]
Linggi, M.S.; Burke, T.L.; Williams, B.B.; Harrington, A.; Kraemer, R.; Hempstead, B.L.; Yoon, S.O.; Carter, B.D. Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor. J. Biol. Chem., 2005, 280(14), 13801-13808.
[39]
Chen, C.; Shin, J.H.; Eggold, J.T.; Chung, M.K.; Zhang, L.H.; Lee, J.; Sunwoo, J.B. ESM1 mediates NGFR-induced invasion and metastasis in murine oral squamous cell carcinoma. Oncotarget, 2016, 7(43), 70738-70749.
[40]
Zhu, Y.; Zhang, X.; Qi, L.; Cai, Y.; Yang, P.; Xuan, G.; Jiang, Y. HULC long noncoding RNA silencing suppresses angiogenesis by regulating ESM-1 via the PI3K/Akt/mTOR signaling pathway in human gliomas. Oncotarget, 2016, 7(12), 14429-14440.
[41]
Matano, F.; Yoshida, D.; Ishii, Y.; Tahara, S.; Teramoto, A.; Morita, A. Endocan, a new invasion and angiogenesis marker of pituitary adenomas. J. Neurooncol., 2014, 117(3), 485-491.
[42]
Priya, M.K.; Sahu, G.; Soto-Pantoja, D.R.; Goldy, N.; Sundaresan, A.M.; Jadhav, V.; Barathkumar, T.R.; Saran, U.; Jaffar Ali, B.M.; Roberts, D.D.; Bera, A.K.; Chatterjee, S. Tipping off endothelial tubes: nitric oxide drives tip cells. Angiogenesis, 2015, 18(2), 175-189.
[43]
Rocha, S.F.; Schiller, M.; Jing, D.; Li, H.; Butz, S.; Vestweber, D.; Biljes, D.; Drexler, H.C.A.; Nieminen-Kelhä, M.; Vajkoczy, P.; Adams, S.; Benedito, R.; Adams, R.H. Esm1 modulates endothelial tip cell behavior and vascular permeability by enhancing VEGF bioavailability. Circ. Res., 2014, 115(6), 581-590.
[44]
Su, T.; Zhong, Y.; Demetriades, A.M.; Shen, J.; Sui, A.; Yao, Y.; Gao, Y.; Zhu, Y.; Shen, X.; Xie, B. Endocan blockade suppresses experimental ocular neovascularization in mice. Invest. Ophthalmol. Vis. Sci., 2018, 59(2), 930-939.
[45]
Leroy, X.; Aubert, S.; Zini, L.; Franquet, H.; Kervoaze, G.; Villers, A.; Delehedde, M.; Copin, M.C.; Lassalle, P. Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma. Histopathology, 2010, 56(2), 180-187.
[46]
Turner, H.E.; Harris, A.L.; Melmed, S.; Wass, J.A.H. Angiogenesis in endocrine tumors. Endocr. Rev., 2003, 24(5), 600-632.
[47]
Almog, N.; Ma, L.; Raychowdhury, R.; Schwager, C.; Erber, R.; Short, S.; Hlatky, L.; Vajkoczy, P.; Huber, P.E.; Folkman, J.; Abdollahi, A. Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. Cancer Res., 2009, 69(3), 836-844.
[48]
Italiano, J.E., Jr; Richardson, J.L.; Patel-Hett, S.; Battinelli, E.; Zaslavsky, A.; Short, S.; Ryeom, S.; Folkman, J.; Klement, G.L. Angiogenesis is regulated by a novel mechanism: Pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood, 2008, 111(3), 1227-1233.
[50]
Parant, O.; Dubernard, G.; Challier, J.C.; Oster, M.; Uzan, S.; Aractingi, S.; Khosrotehrani, K. CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers. Lab. Invest., 2009, 89(8), 915-923.
[51]
Müller, A.M.; Hermanns, M.I.; Skrzynski, C.; Nesslinger, M.; Müller, K.M.; Kirkpatrick, C.J. Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in vitro. Exp. Mol. Pathol., 2002, 72(3), 221-229.
[52]
Nielsen, J.S.; McNagny, K.M. CD34 is a key regulator of hematopoietic stem cell trafficking to bone marrow and mast cell progenitor trafficking in the periphery. Microcirculation, 2009, 16(6), 487-496.
[53]
Asa, S.L.; Ezzat, S. The pathogenesis of pituitary tumors. Annu. Rev. Pathol., 2009, 4(4), 97-126.
[54]
Kong, Y.G.; Ren, Z.Y.; Su, C.B.; Wang, R.Z.; Ma, W.B.; Lian, W. Elevated soluble epidermal growth factor receptor level in pituitary adenoma and carcinoma. Chin. Med. Sci. J., 2004, 19(3), 199-202.
[55]
Zuo, L.; Zhang, S.M.; Hu, R.L.; Zhu, H.Q.; Zhou, Q.; Gui, S.Y.; Wu, Q.; Wang, Y. Correlation between expression and differentiation of endocan in colorectal cancer. World J. Gastroenterol., 2008, 14(28), 4562-4568.
[56]
Zhang, S.; Zuo, L.; Gui, S.; Zhou, Q.; Wei, W.; Wang, Y. Induction of cell differentiation and promotion of endocan gene expression in stomach cancer by melatonin. Mol. Biol. Rep., 2012, 39(3), 2843-2849.
[57]
Sun, H.; Zhang, H.; Li, K.; Wu, H.; Zhan, X.; Fang, F.; Qin, Y.; Wei, Y. ESM-1 promotes adhesion between monocytes and endothelial cells under intermittent hypoxia. J. Cell. Physiol., 2019, 234(2), 1512-1521.
[58]
Zhang, Y.W.; Su, Y.; Volpert, O.V.; Vande Woude, G.F. Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc. Natl. Acad. Sci. USA, 2003, 100(22), 12718-12723.
[59]
Delehedde, M.; Devenyns, L.; Maurage, C.A.; Vivès, R.R. Endocan in cancers: A lesson from a circulating dermatan sulfate proteoglycan. Int. J. Cell Biol., 2013, 2013 705027
[60]
Olsson, A.K.; Dimberg, A.; Kreuger, J.; Claesson-Welsh, L. VEGF receptor signalling - in control of vascular function. Nat. Rev. Mol. Cell Biol., 2006, 7(5), 359-371.
[61]
Kang, Y.H.; Ji, N.Y.; Han, S.R.; Lee, C.I.; Kim, J.W.; Yeom, Y.I.; Kim, Y.H.; Chun, H.K.; Kim, J.W.; Chung, J.W.; Ahn, D.K.; Lee, H.G.; Song, E.Y. ESM-1 regulates cell growth and metastatic process through activation of NF-κB in colorectal cancer. Cell. Signal., 2012, 24(10), 1940-1949.
[62]
Kang, Y.H.; Ji, N.Y.; Lee, C.I.; Lee, H.G.; Kim, J.W.; Yeom, Y.I.; Kim, D.G.; Yoon, S.K.; Kim, J.W.; Park, P.J.; Song, E.Y. ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma. Amino Acids, 2011, 40(3), 1003-1013.
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Current Cancer Therapy Reviews
Current Drug Safety
Current Drug Targets
Recent Patents on Anti-Cancer Drug Discovery
Letters in Drug Design & Discovery
Current Drug Discovery Technologies
Current Radiopharmaceuticals
Related Books
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Clinical Drug Research - Anti-Cancer Agents
Advances in Organic Synthesis
Frontiers in Natural Product Chemistry
Recent Advances in Analytical Techniques
Frontiers in Drug Design and Discovery
NEOPLASIA and FERTILITY
Therapeutic Use of Plant Secondary Metabolites
Frontiers in Computational Chemistry
Frontiers in Bioactive Compounds
Article Metrics
75
11