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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Development and Characterization of Novel Chronic Eosinophilic Inflammation- Mediated Murine Model of Malignant Pancreatitis

Author(s): Hemanth Kumar Kandikattu, Sathisha Upparahalli Venkateshaiah, Chandra Sekhar Yadavalli, Lokanatha Oruganti and Anil Mishra*

Volume 23, Issue 10, 2023

Published on: 28 April, 2023

Page: [1303 - 1317] Pages: 15

DOI: 10.2174/1871530322666220804104224

Price: $65

Abstract

Aims: Develop a novel murine models of malignant pancreatitis.

Background: Although patients with chronic pancreatitis are at a greater risk of developing pancreatic cancer, there is no definitive mouse model that currently develops chronic pancreatitis-induced pancreatic cancer.

Objective: Characterization of eosinophilic inflammation-mediated malignant pancreatitis in novel murine model.

Methods: We developed a murine model of chronic eosinophilic inflammation associated with pancreatitis that also shows characteristic features of pancreatic malignancy. The mouse received cerulein and azoxymethane via intraperitoneal administration developed pathological malignant phenotype, as well as concomitant lung inflammation.

Results: We discovered pathological alterations in the pancreas that were associated with chronic pancreatitis, including a buildup of eosinophilic inflammation. Eosinophil degranulation was reported nearby in the pancreas tissue sections that show acinar-to-ductal metaplasia and acinar cell atrophy, both of which are characteristic of pancreatic malignancies. Additionally, we also observed the formation of PanIN lesions after three initial doses of AOM and eight weeks of cerulein with the AOM treatment regimen. We discovered that persistent pancreatic eosinophilic inflammation linked with a pancreatic malignant phenotype contributes to pulmonary damage. The RNA seq analysis also confirmed the induction of fibro-inflammatory and oncogenic proteins in pancreas and lung tissues. Further, in the current manuscript, we now report the stepwise kinetically time-dependent cellular inflammation, genes and proteins involved in the development of pancreatitis malignancy and associated acute lung injury by analyzing the mice of 3 AOM with 3, 8, and 12 weeks of the cerulein challenged protocol regime.

Conclusion: We first show that sustained long-term eosinophilic inflammation induces time-dependent proinflammatory, profibrotic and malignancy-associated genes that promote pancreatic malignancy and acute lung injury in mice.

Keywords: Acute lung injury, Azoxymethane, Cerulein, Chronic pancreatitis, Eosinophils, Fibrosis, Malignancy

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[1]
Beyer, G.; Habtezion, A.; Werner, J.; Lerch, M.M.; Mayerle, J. Chronic pancreatitis. Lancet, 2020, 396(10249), 499-512.
[http://dx.doi.org/10.1016/S0140-6736(20)31318-0] [PMID: 32798493]
[2]
Shields, C.J.; Winter, D.C.; Redmond, H.P. Lung injury in acute pancreatitis: Mechanisms, prevention, and therapy. Curr. Opin. Crit. Care, 2002, 8(2), 158-163.
[http://dx.doi.org/10.1097/00075198-200204000-00012] [PMID: 12386518]
[3]
Manohar, M.; Verma, A.K.; Venkateshaiah, S.U.; Mishra, A. Role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Am. J. Physiol. Gastrointest. Liver Physiol., 2018, 314(2), G211-G222.
[http://dx.doi.org/10.1152/ajpgi.00210.2017] [PMID: 28935682]
[4]
Kandikattu, H.K.; Venkateshaiah, S.U.; Mishra, A. Chronic pancreatitis and the development of pancreatic cancer. Endocr. Metab. Immune Disord. Drug Targets, 2020, 20(8), 1182-1210.
[5]
Manohar, M.; Verma, A.K.; Upparahalli Venkateshaiah, S.; Goyal, H.; Mishra, A. Food-induced acute pancreatitis. Dig. Dis. Sci., 2017, 62(12), 3287-3297.
[http://dx.doi.org/10.1007/s10620-017-4817-2] [PMID: 29086330]
[6]
Tian, L.; Lu, Z.-P.; Cai, B.-B.; Zhao, L.-T.; Qian, D.; Xu, Q.-C.; Wu, P-F.; Zhu, Y.; Zhang, J.-J.; Du, Q.; Miao, Y.; Jiang, K.R. Activation of pancreatic stellate cells involves an EMT-like process. Int. J. Oncol., 2016, 48(2), 783-792.
[http://dx.doi.org/10.3892/ijo.2015.3282] [PMID: 26647741]
[7]
Jaidev, L.; Chede, L.S.; Kandikattu, H.K. Theranostic nanoparticles for pancreatic cancer treatment. Endocr. Metab. Immune Disord. Drug Targets, 2021, 21(2), 203-214.
[PMID: 32416712]
[8]
Gitto, S.B.; Beardsley, J.M.; Nakkina, S.P.; Oyer, J.L.; Cline, K.A.; Litherland, S.A.; Copik, A.J.; Khaled, A.S.; Fanaian, N.; Arnoletti, J.P.; Altomare, D.A. Identification of a novel IL-5 signaling pathway in chronic pancreatitis and crosstalk with pancreatic tumor cells. Cell Commun. Signal., 2020, 18(1), 95.
[http://dx.doi.org/10.1186/s12964-020-00594-x] [PMID: 32552827]
[9]
Manohar, M.; Verma, A.K.; Venkateshaiah, S.U.; Mishra, A. Significance of eosinophils in promoting pancreatic malignancy. J. Gastroenterol. Pancreatol. Liver Disord., 2017, 5(1), 10.
[http://dx.doi.org/10.15226/2374-815X/5/1/001109] [PMID: 29756031]
[10]
Storz, P. Acinar cell plasticity and development of pancreatic ductal adenocarcinoma. Nat. Rev. Gastroenterol. Hepatol., 2017, 14(5), 296-304.
[http://dx.doi.org/10.1038/nrgastro.2017.12] [PMID: 28270694]
[11]
Venkateshaiah, S.U.; Mishra, A.; Manohar, M.; Verma, A.K.; Rajavelu, P.; Niranjan, R.; Wild, L.G.; Parada, N.A.; Blecker, U.; Lasky, J.A.; Mishra, A. A critical role for IL-18 in transformation and maturation of naive eosinophils to pathogenic eosinophils. J. Allergy Clin. Immunol., 2018, 142(1), 301-305.
[http://dx.doi.org/10.1016/j.jaci.2018.02.011] [PMID: 29499224]
[12]
Yadav, D.; Timmons, L.; Benson, J.T.; Dierkhising, R.A.; Chari, S.T. Incidence, prevalence, and survival of chronic pancreatitis: A population-based study. Am. J. Gastroenterol., 2011, 106(12), 2192-2199.
[http://dx.doi.org/10.1038/ajg.2011.328] [PMID: 21946280]
[13]
Frumkin, H. Agent orange and cancer: An overview for clinicians. CA Cancer J. Clin., 2003, 53(4), 245-255.
[http://dx.doi.org/10.3322/canjclin.53.4.245] [PMID: 12924777]
[14]
National Academies of Sciences. Medicine. Veterans and Agent Orange: Update 11. The National Academies Press: Washington, DC, USA, 2018.
[15]
Clapper, M.L.; Cooper, H.S.; Chang, W.C. Dextran sulfate sodium-induced colitis-associated neoplasia: A promising model for the development of chemopreventive interventions. Acta Pharmacol. Sin., 2007, 28(9), 1450-1459.
[http://dx.doi.org/10.1111/j.1745-7254.2007.00695.x] [PMID: 17723178]
[16]
Schmidt, J.; Compton, C.C.; Rattner, D.W.; Lewandrowski, K.; Warshaw, A.L. Late histopathologic changes and healing in an improved rodent model of acute necrotizing pancreatitis. Digestion, 1995, 56(3), 246-252.
[http://dx.doi.org/10.1159/000201251] [PMID: 7544747]
[17]
Iwanaga, N.; Sandquist, I.; Wanek, A.; McCombs, J.; Song, K.; Kolls, J.K. Host immunology and rational immunotherapy for carbapenem-resistant Klebsiella pneumoniae infection. JCI Insight, 2020, 5(8), 5.
[http://dx.doi.org/10.1172/jci.insight.135591] [PMID: 32213713]
[18]
Steele, C.W.; Karim, S.A.; Leach, J.D.G.; Bailey, P.; Upstill-Goddard, R.; Rishi, L.; Foth, M.; Bryson, S.; McDaid, K.; Wilson, Z.; Eberlein, C.; Candido, J.B.; Clarke, M.; Nixon, C.; Connelly, J.; Jamieson, N.; Carter, C.R.; Balkwill, F.; Chang, D.K.; Evans, T.R.J.; Strathdee, D.; Biankin, A.V.; Nibbs, R.J.B.; Barry, S.T.; Sansom, O.J.; Morton, J.P. CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell, 2016, 29(6), 832-845.
[http://dx.doi.org/10.1016/j.ccell.2016.04.014] [PMID: 27265504]
[19]
Jiang, S.; Wang, Q.; Wang, Y.; Song, X.; Zhang, Y. Blockade of CCL2/CCR2 signaling pathway prevents inflammatory monocyte recruitment and attenuates OVA-Induced allergic asthma in mice. Immunol. Lett., 2019, 214, 30-36.
[http://dx.doi.org/10.1016/j.imlet.2019.08.006] [PMID: 31454522]
[20]
Wang, L.; Wang, L.; Wang, S.; Zhou, Z.; Liu, Z.; Xu, P.; Luo, X.; Wu, T.; Luo, F.; Yan, J. N2E4, a monoclonal antibody targeting neuropilin-2, inhibits tumor growth and metastasis in pancreatic ductal adenocarcinoma via suppressing FAK/Erk/HIF-1α signaling. Front. Oncol., 2021, 11, 657008.
[http://dx.doi.org/10.3389/fonc.2021.657008]
[21]
Kandikattu, H.K.; Manohar, M.; Verma, A.K.; Kumar, S.; Yadavalli, C.S.; Upparahalli Venkateshaiah, S.; Mishra, A. Macrophages-induced IL-18-mediated eosinophilia promotes characteristics of pancreatic malignancy. Life Sci. Alliance, 2021, 4(8), 4.
[http://dx.doi.org/10.26508/lsa.202000979] [PMID: 34183442]
[22]
Djurec, M.; Graña, O.; Lee, A.; Troulé, K.; Espinet, E.; Cabras, L.; Navas, C.; Blasco, M.T.; Martín-Díaz, L.; Burdiel, M.; Li, J.; Liu, Z.; Vallespinós, M.; Sanchez-Bueno, F.; Sprick, M.R.; Trumpp, A.; Sainz, B., Jr; Al-Shahrour, F.; Rabadan, R.; Guerra, C.; Barbacid, M. Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors. Proc. Natl. Acad. Sci. USA, 2018, 115(6), E1147-E1156.
[http://dx.doi.org/10.1073/pnas.1717802115] [PMID: 29351990]
[23]
Guo, Q.; Chu, Y.; Li, H.; Shi, D.; Lin, L.; Lan, W.; Wu, D. Dickkopf-related protein 3 alters aerobic glycolysis in pancreatic cancer BxPC-3 cells, promoting CD4+ T-cell activation and function. Eur. J. Med. Res., 2021, 26(1), 93.
[http://dx.doi.org/10.1186/s40001-021-00567-x] [PMID: 34391478]
[24]
Cheng, L.-C.; Chao, Y.-J.; Overman, M.J.; Wang, C.-Y.; Phan, N.N.; Chen, Y.-L.; Wang, T.-W.; Hsu, H.-P.; Shan, Y.-S.; Lai, M.-D. Increased expression of secreted frizzled related protein 1 (SFRP1) predicts ampullary adenocarcinoma recurrence. Sci. Rep., 2020, 10(1), 13255.
[http://dx.doi.org/10.1038/s41598-020-69899-8] [PMID: 32764696]
[25]
Chen, K-L.; Lv, Z-Y.; Yang, H-W.; Liu, Y.; Long, F-W.; Zhou, B.; Sun, X-F.; Peng, Z-H.; Zhou, Z-G.; Li, Y. Effects of tocilizumab on experimental severe acute pancreatitis and associated acute lung injury. Crit. Care Med., 2016, 44(8), e664-e677.
[http://dx.doi.org/10.1097/CCM.0000000000001639] [PMID: 26963319]
[26]
Fallon, H.; Tollerud, D.; Breslow, N. Veterans and agent orange: Health effects of herbicides used in Vietnam. In: Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides; National Academic Press: Washington, DC, USA, 1994.
[27]
Venkateshaiah, S.U.; Zhu, X.; Rajavelu, P.; Niranjan, R.; Manohar, M.; Verma, A.K.; Lasky, J.A.; Mishra, A. Regulatory effects of IL-15 on allergen-induced airway obstruction. J. Allergy Clin. Immunol., 2018, 141, 906-917.
[28]
Kandikattu, H.K.; Upparahalli Venkateshaiah, S.; Mishra, A. Synergy of Interleukin (IL)-5 and IL-18 in eosinophil mediated pathogenesis of allergic diseases. Cytokine Growth Factor Rev., 2019, 47, 83-98.
[http://dx.doi.org/10.1016/j.cytogfr.2019.05.003] [PMID: 31126874]
[29]
Yanagawa, M.; Uchida, K.; Ando, Y.; Tomiyama, T.; Yamaguchi, T.; Ikeura, T.; Fukui, T.; Nishio, A.; Uemura, Y.; Miyara, T.; Okamoto, H.; Satoi, S.; Okazaki, K. Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis. J. Gastroenterol., 2018, 53(3), 449-460.
[http://dx.doi.org/10.1007/s00535-017-1390-6] [PMID: 28921377]
[30]
Kandikattu, H.K.; Manohar, M.; Upparahalli Venkateshaiah, S.; Yadavalli, C.; Mishra, A. Chronic inflammation promotes epithelial-mesenchymal transition-mediated malignant phenotypes and lung injury in experimentally-induced pancreatitis. Life Sci., 2021, 278, 119640.
[http://dx.doi.org/10.1016/j.lfs.2021.119640] [PMID: 34048812]
[31]
Ramachandran, V.; Arumugam, T.; Wang, H.; Logsdon, C.D. Anterior gradient 2 is expressed and secreted during the development of pancreatic cancer and promotes cancer cell survival. Cancer Res., 2008, 68(19), 7811-7818.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1320] [PMID: 18829536]
[32]
Zhou, L.; Husted, H.; Moore, T.; Lu, M.; Deng, D.; Liu, Y.; Ramachandran, V.; Arumugam, T.; Niehrs, C.; Wang, H.; Chiao, P.; Ling, J.; Curran, M.A.; Maitra, A.; Hung, M.C.; Lee, J.E.; Logsdon, C.D.; Hwang, R.F. Suppression of stromal-derived Dickkopf-3 (DKK3) inhibits tumor progression and prolongs survival in pancreatic ductal adenocarcinoma. Sci. Transl. Med., 2018, 10(464), 10.
[http://dx.doi.org/10.1126/scitranslmed.aat3487] [PMID: 30355799]
[33]
Sun, L.; Zhang, Y.; Zhang, C. Distinct expression and prognostic value of MS4A in gastric cancer. Open Med. (Wars.), 2018, 13, 178-188.
[http://dx.doi.org/10.1515/med-2018-0028] [PMID: 29756054]
[34]
Yu, S.; Wu, Y.; Li, C.; Qu, Z.; Lou, G.; Guo, X.; Ji, J.; Li, N.; Guo, M.; Zhang, M.; Lei, L.; Tai, S. Comprehensive analysis of the SLC16A gene family in pancreatic cancer via integrated bioinformatics. Sci. Rep., 2020, 10(1), 7315.
[http://dx.doi.org/10.1038/s41598-020-64356-y] [PMID: 32355273]
[35]
Li, Q.; Yin, L.; Jones, L.W.; Chu, G.C.; Wu, J.B.; Huang, J-M.; Li, Q.; You, S.; Kim, J.; Lu, Y-T.; Mrdenovic, S.; Wang, R.; Freeman, M.R.; Garraway, I.; Lewis, M.S.; Chung, L.W.; Zhau, H.E. Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells. Oncotarget, 2016, 7(51), 84645-84657.
[http://dx.doi.org/10.18632/oncotarget.13175] [PMID: 27835867]
[36]
Johnston, J.R.; Chase, P.B.; Pinto, J.R. Troponin through the looking-glass: Emerging roles beyond regulation of striated muscle contraction. Oncotarget, 2017, 9(1), 1461-1482.
[http://dx.doi.org/10.18632/oncotarget.22879] [PMID: 29416706]
[37]
Halvorsen, O.J.; Rostad, K.; Øyan, A.M.; Puntervoll, H.; Bø, T.H.; Stordrange, L.; Olsen, S.; Haukaas, S.A.; Hood, L.; Jonassen, I.; Kalland, K.H.; Akslen, L.A. Increased expression of SIM2-s protein is a novel marker of aggressive prostate cancer. Clin. Cancer Res., 2007, 13(3), 892-897.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1207] [PMID: 17289882]
[38]
Mardin, W.A.; Ntalos, D.; Mees, S.T.; Spieker, T.; Senninger, N.; Haier, J.; Dhayat, S.A. SERPINB5 promoter hypomethylation differentiates pancreatic ductal adenocarcinoma from pancreatitis. Pancreas, 2016, 45(5), 743-747.
[http://dx.doi.org/10.1097/MPA.0000000000000526] [PMID: 26646275]
[39]
Ruckert, M.T.; de Andrade, P.V.; Santos, V.S.; Silveira, V.S. Protein tyrosine phosphatases: Promising targets in pancreatic ductal adenocarcinoma. Cell. Mol. Life Sci., 2019, 76(13), 2571-2592.
[http://dx.doi.org/10.1007/s00018-019-03095-4] [PMID: 30982078]
[40]
Chen, J.; Zhu, X-X.; Xu, H.; Fang, H-Z.; Zhao, J-Q. Expression and prognostic significance of unique ULBPs in pancreatic cancer. OncoTargets Ther., 2016, 9, 5271-5279.
[http://dx.doi.org/10.2147/OTT.S107771] [PMID: 27621649]
[41]
Rong, Y.; Jin, D.; Hou, C.; Hu, J.; Wu, W.; Ni, X.; Wang, D.; Lou, W. Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2. BMC Gastroenterol., 2010, 10, 68.
[http://dx.doi.org/10.1186/1471-230X-10-68] [PMID: 20587030]
[42]
Chen, S.; Gao, C.; Yu, T.; Qu, Y.; Xiao, G.G.; Huang, Z. Bioinformatics analysis of a prognostic miRNA signature and potential key genes in pancreatic cancer. Front. Oncol., 2021, 11641289.
[http://dx.doi.org/10.3389/fonc.2021.641289] [PMID: 34094925]
[43]
Chen, J.; Wu, W.; Chen, L.; Zhou, H.; Yang, R.; Hu, L.; Zhao, Y. Profiling the potential tumor markers of pancreatic ductal adenocarcinoma using 2D-DIGE and MALDI-TOF-MS: Up-regulation of Complement C3 and alpha-2-HS-glycoprotein. Pancreatology, 2013, 13(3), 290-297.
[http://dx.doi.org/10.1016/j.pan.2013.03.010] [PMID: 23719603]
[44]
Liu, X.; Wang, J.; Wang, H.; Yin, G.; Liu, Y.; Lei, X.; Xiang, M. REG3A accelerates pancreatic cancer cell growth under IL-6-associated inflammatory condition: Involvement of a REG3A-JAK2/STAT3 positive feedback loop. Cancer Lett., 2015, 362(1), 45-60.
[http://dx.doi.org/10.1016/j.canlet.2015.03.014] [PMID: 25779676]
[45]
Zhang, H.; Corredor, A.L.G.; Messina-Pacheco, J.; Li, Q.; Zogopoulos, G.; Kaddour, N.; Wang, Y.; Shi, B.Y.; Gregorieff, A.; Liu, J.L.; Gao, Z.H. REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway. Commun. Biol., 2021, 4(1), 688.
[http://dx.doi.org/10.1038/s42003-021-02193-z] [PMID: 34099862]
[46]
Sanford, D.E.; Belt, B.A.; Panni, R.Z.; Mayer, A.; Deshpande, A.D.; Carpenter, D.; Mitchem, J.B.; Plambeck-Suess, S.M.; Worley, L.A.; Goetz, B.D.; Wang-Gillam, A.; Eberlein, T.J.; Denardo, D.G.; Goedegebuure, S.P.; Linehan, D.C. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: A role for targeting the CCL2/CCR2 axis. Clin. Cancer Res., 2013, 19(13), 3404-3415.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0525] [PMID: 23653148]
[47]
Dallas, N.A.; Gray, M.J.; Xia, L.; Fan, F.; van Buren, G., II; Gaur, P.; Samuel, S.; Lim, S.J.; Arumugam, T.; Ramachandran, V.; Wang, H.; Ellis, L.M. Neuropilin-2-mediated tumor growth and angiogenesis in pancreatic adenocarcinoma. Clin. Cancer Res., 2008, 14(24), 8052-8060.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1520] [PMID: 19088020]
[48]
Heinrich, E.L.; Lee, W.; Lu, J.; Lowy, A.M.; Kim, J. Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in pancreatic cancer cells. J. Transl. Med., 2012, 10, 68.
[http://dx.doi.org/10.1186/1479-5876-10-68] [PMID: 22472349]
[49]
Park, J.W.; Choi, J.S.; Han, K.J.; Lee, S.H.; Kim, E.J.; Cho, J.H. Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group. Korean J. Intern. Med. (Korean. Assoc. Intern. Med.), 2018, 33(6), 1103-1110.
[http://dx.doi.org/10.3904/kjim.2017.133] [PMID: 29117667]
[50]
Feng, L.; Qi, Q.; Wang, P.; Chen, H.; Chen, Z.; Meng, Z.; Liu, L. Serum level of CCL2 predicts outcome of patients with pancreatic cancer. Acta Gastroenterol. Belg., 2020, 83(2), 295-299.
[PMID: 32603049]
[51]
Huang, X.; Zhang, G.; Liang, T. Pancreatic tumor initiation: The potential role of IL-33. Signal Transduct. Target. Ther., 2021, 6(1), 204.
[http://dx.doi.org/10.1038/s41392-021-00636-x] [PMID: 34023857]
[52]
Li, Y.; Zeng, M.; Wang, T.; Jiang, F. COL5A3 is a prognostic biomarker and correlated with immune infiltrates in pancreatic cancer. Research Square, 2021.
[53]
Chen, S.; Huang, F.; Chen, S.; Chen, Y.; Li, J.; Li, Y.; Lian, G.; Huang, K. Bioinformatics-based identification of tumor microenvironment-related prognostic genes in pancreatic cancer. Front. Genet., 2021, 12, 632803.
[http://dx.doi.org/10.3389/fgene.2021.632803] [PMID: 34276760]
[54]
Chen, S-H.; Hung, W-C.; Wang, P.; Paul, C.; Konstantopoulos, K. Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation. Sci. Rep., 2013, 3, 1870.
[http://dx.doi.org/10.1038/srep01870] [PMID: 23694968]
[55]
Nukarinen, E.; Lindström, O.; Kuuliala, K.; Kylänpää, L.; Pettilä, V.; Puolakkainen, P.; Kuuliala, A.; Hämäläinen, M.; Moilanen, E.; Repo, H.; Hästbacka, J. Association of matrix metalloproteinases-7,-8 and-9 and TIMP-1 with disease severity in acute pancreatitis. A cohort study. PLoS One, 2016, 11(8), e0161480.
[http://dx.doi.org/10.1371/journal.pone.0161480] [PMID: 27561093]
[56]
Liu, Y.; Li, F.; Gao, F.; Xing, L.; Qin, P.; Liang, X.; Zhang, J.; Qiao, X.; Lin, L.; Zhao, Q.; Du, L. Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling. Oncotarget, 2016, 7(26), 40148-40159.
[http://dx.doi.org/10.18632/oncotarget.9512] [PMID: 27223086]
[57]
El-Hariry, I.; Pignatelli, M.; Lemoine, N.R. FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pancreatic adenocarcinoma cell lines. Br. J. Cancer, 2001, 84(12), 1656-1663.
[http://dx.doi.org/10.1054/bjoc.2001.1813] [PMID: 11401320]
[58]
Liang, C.; Xu, J.; Meng, Q.; Zhang, B.; Liu, J.; Hua, J.; Zhang, Y.; Shi, S.; Yu, X. TGFB1-induced autophagy affects the pattern of pancreatic cancer progression in distinct ways depending on SMAD4 status. Autophagy, 2020, 16(3), 486-500.
[http://dx.doi.org/10.1080/15548627.2019.1628540] [PMID: 31177911]

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