ROLE OF MICROENVIRONMENT IN THE DEVELOPMENT AND PROGRESSION OF PANCREATIC CANCER
https://doi.org/10.21294/1814-4861-2016-15-3-85-92
Abstract
Pancreatic cancer is a highly aggressive malignancy with metastatic potential and poor response to chemotherapy. Unfortunately, molecular-based targeted therapies failed to make significant progress against pancreatic cancer. One of the promising subjects of molecular oncology is the study of tumor microenvironment modulation for therapeutic purposes. In the present review, the description of pancreatic cancer microenvironment is provided, including intercellular interaction regulation which is important for tumor growth and progression. The study of this topic is important for the development of new therapies for pancreatic cancer.
About the Authors
E. V. Okladnikova
Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky
Russian Federation
MD, PhD, Associate Professor, Department of Pharmacology
Russian Federation
MD, PhD, Associate Professor, Department of Pharmacology
T. G> Ruksha
Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenetsky
Russian Federation
MD, DSc, Head of the Department of Pathological Physiology
Russian Federation
MD, DSc, Head of the Department of Pathological Physiology
References
1. El’nikova A.A. Tumor microenvironment a dark horse in anticancer chemotherapy // Zdorov’e i obrazovanie v XXI veke. 2015. Vol. 17 (1). P. 84–86. [in Russian]
2. Monastyrskaya E.A., Lyamina S.V., Malyshev I.Yu. Ml and М2 phenotypes of activated macrophages and their role in immune response and pathology. Patogenez. 2008. Vol. 6 (4). P. 31–39. [in Russian]
3. The state of cancer care in Russia in 2013 / Eds A.D. Kaprin, V.V. Starinskij, G.V. Petrova. M., 2014. 235 p. [in Russian]
4. Alachkar H., Santhanam R., Maharry K., Metzeler K.H., Huang X., Kohlschmidt J., Mendler J.H., Benito J.M., Hickey C., Neviani P., Dorrance A.M., Anghelina M., Khalife J., Tarighat S.S.,Volinia S., Whitman S.P., Paschka P., Hoellerbauer P., Wu Y.Z., Han L., BolonB.N., BlumW., Mrózek K., Carroll A.J., Perrotti D., Andreeff M., Caligiuri M.A., Konopleva M., Garzon R., Bloomfield C.D, Marcucci G. SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome // J. Clin. Invest. 2014. Vol. 124 (4). P. 1512–1524. doi: 10.1172/JCI70921.
5. Apte M.V., Pirola R.C., Wilson J.S. The fibrosis of chronic pancreatitis: new insights into the role of pancreatic stellate cells //Antioxid. Redox. Signal. 2011. Vol. 15 (10). P. 2711–2722. doi: 10.1089/ars.2011.4079.
6. Apte M.V., Xu Z., Pothula S., Goldstein D., Pirola R.C., Wilson J.S. Pancreatic cancer: The microenvironment needs attention too! // Pancreatology. 2015. Vol. 15 (4 Suppl). S. 32–38. doi: 10.1016/j.pan.2015.02.013.
7. Apte M.V., Wilson J.S., Lugea A., Pandol S.J. A starring role for stellate cells in the pancreatic cancer microenvironment // Gastroenterology. 2013. Vol. 144 (6). P. 1210–1219. doi: 10.1053/j.gastro.2012.11.037.
8. Berchtold S., Grünwald B., Krüger A., Reithmeier A., Hähl T.,Cheng T., Feuchtinger A., Born D., Erkan M., Kleeff J., Esposito I. Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma // Cancer Lett. 2015. Vol. 356 (2 Pt B). P. 721–732. doi: 10.1016/j.canlet.2014.10.020.
9. Bosco M.C., Puppo M., Blengio F., Fraone T., Cappello P., Giovarelli M., Varesio L. Monocytes and dendritic cells in a hypoxic environment: Spotlights on chemotaxis and migration // Immunobiology. 2008. Vol. 213 (9–10). P. 733–749. doi: 10.1016/j.imbio.2008.07.031.
10. Brandes F., Schmidt K., Wagner C., Redekopf J., Schlitt H.J., Geissler E.K., Lang S.A. Targeting cMET with INC280 impairs tumour growth and improves efficacy of gemcitabine in a pancreatic cancer model // BMC Cancer. 2015. Vol. 15. P. 71. doi: 10.1186/s12885-015-1064-9.
11. Brennen W.N., Isaacs J.T., Denmeade S.R. Rationale behind targeting fibroblast activation protein-expressing carcinoma-associated fibroblasts as a novel chemotherapeutic strategy // Mol. Cancer Ther. 2012. Vol. 11 (2). P. 257–266. doi: 10.1158/1535-7163.MCT-11-0340.
12. Brentnall T.A. Arousal of cancer-associated stromal fibroblasts: palladin-activated fibroblasts promote tumor invasion // Cell Adh. Migr. 2012. Vol. 6 (6). P. 488–494. doi: 10.4161/cam.21453.
13. Buscail L., Bournet B., Dufresne M., Torrisani J., Cordelier P. Advance in the biology of pancreatic of cancer // Bull. Cancer. 2015. Vol. 102 (6 Suppl 1). S53-61. doi: 10.1016/S0007-4551(15)31218-2.
14. Casazza A., Laoui D., Wenes M., Rizzolio S., Bassani N., Mambretti M., Deschoemaeker S., Van Ginderachter J.A., Tamagnone L., Mazzone M. Impeding macrophage entry into hypoxic tumor areas by Sema3A/ Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity // Cancer Cell. 2013. Vol. 24 (6). P. 695–709. doi: 10.1016/j. ccr.2013.11.007.
15. Cid-Arregui A., Juarez V. Perspectives in the treatment of pancreatic adenocarcinoma // World J. Gastroenterol. 2015. Vol. 21 (31). P. 9297–9316. doi: 10.3748/wjg.v21.i31.9297.
16. Chiorean E.G., Coveler A.L. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies // Drug Des. Devel. Ther. 2015. Vol. 9. P. 3529–3545. doi: 10.2147/DDDT.S60328.
17. Cohen R., Neuzillet C., Tijeras-Raballand A., Faivre S., de Gramont A., Raymond E. Targeting cancer cell metabolism in pancreatic adenocarcinoma // Oncotarget. 2015. Vol. 6 (19). P. 16832–16847.
18. Coleman S.J., Chioni A.M., Ghallab M., Anderson R.K., Lemoine N.R., Kocher H.M., Grose R.P. Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion // EMBO Mol. Med. 2014. Vol. 6 (4). P. 467–481. doi: 10.1002/emmm. 201302698.
19. Dangi-Garimella S., Sahai V., Ebine K., Kumar K., Munshi H.G. Three-dimensional collagen I promotes gemcitabine resistance in vitro in pancreatic cancer cells through HMGA2-dependent histone acetyltransferase expression // PLoS One. 2013. Vol. 8 (5):e64566. doi: 10.1371/journal.pone.0064566.
20. Delitto D., Vertes-George E., Hughes S.J., Behrns K.E., Trevino J.G. C-Met signaling in the development of tumorigenesis and chemoresistance: potential applications in pancreatic cancer // World J. Gastroenterol. 2014. Vol. 20 (26). P. 8458–8470. doi: 10.3748/wjg.v20.i26.8458.
21. Drifka C.R., Tod J., Loeffler A.G., Liu Y., Thomas G.J., Eliceiri K.W., Kao W.J. Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis // Mod. Pathol. 2015. Vol. 28 (11). P. 1470–1480. doi: 10.1038/modpathol.2015.97.
22. Erkan M., Kleeff J., Gorbachevski A., Reiser C., Mitkus T., Esposito I., Giese T., Büchler M.W., Giese N.A., Friess H. Periostin creates a tumorsupportive microenvironment in the pancreas by sustaining fibrogenic stellate cell activity // Gastroenterology. 2007. Vol. 132 (4). P. 1447–1464.
23. Feig C., Gopinathan A., Neesse A., Chan D.S., Cook N., Tuveson D.A. The pancreas cancer microenvironment // Clin. Cancer Res. 2012. Vol. 18 (16). P. 4266–4276. doi: 10.1158/1078-0432.CCR-11-3114.
24. Garajová I., Le Large T.Y., Frampton A.E., Rolfo C., Voortman J., Giovannetti E. Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer // Biomed. Res. Int. 2014: 678401. doi: 10.1155/2014/678401.
25. Gardian K., Janczewska S., Olszewski W.L., Durlik M. Analysis of pancreatic cancer microenvironment: role of macrophage infiltrates and growth factors expression // J. Cancer. 2012. Vol. 3. P. 285–291. doi: 10.7150/jca.4537.
26. Hwang R.F., Moore T., Arumugam T., Ramachandran V., Amos K.D., Rivera A, Ji B., Evans D.B., Logsdon C.D. Cancer-associated stromal fibroblasts promote pancreatic tumor progression // Cancer Res. 2008. Vol. 68 (3). P. 918–926. doi: 10.1158/0008-5472.CAN-07-5714.
27. Hu H., Jiao F., Han T., Wang L.W. Functional significance of macrophages in pancreatic cancer biology // Tumour Biol. 2015. doi:10.1007/ s13277-015-4127-2.
28. Infante J.R., Matsubayashi H., Sato N., Tonascia J., Klein A.P., Riall T.A., Yeo C, Iacobuzio-Donahue C., Goggins M. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma // J. Clin Oncol. 2007. Vol. 25 (3). P. 319–325.
29. Ino Y., Yamazaki-Itoh R., Shimada K., Iwasaki M., Kosuge T., Kanai Y., Hiraoka N. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer // Br. J. Cancer. 2013. Vol. 108 (4). P. 914–923. doi: 10.1038/bjc.2013.32.
30. Jacob M., Chang L., Puré E. Fibroblast activation protein in remodeling tissues // Curr. Mol. Med. 2012. Vol. (10). P. 1220–1243.
31. Jacobetz M.A., Chan D.S., Neesse A., Bapiro T.E., Cook N., Frese K.K., Feig C., Nakagawa T., Caldwell M.E., Zecchini H.I., Lolkema M.P., Jiang P., Kultti A., Thompson C.B., Maneval D.C., Jodrell D.I., Frost G.I., Shepard H.M., Skepper J.N., Tuveson D.A. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer // Gut. 2013. Vol. 62 (1). P. 112–120. doi: 10.1136/gutjnl-2012-302529.
32. Kawase T., Yasui Y., Nishina S., Hara Y., Yanatori I., Tomiyama Y., Nakashima Y., Yoshida K., Kishi F., Nakamura M., Hino K. Fibroblast activation protein-α-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma // BMC Gastroenterol. 2015. Vol. 15 (1). P. 109. doi: 10.1186/s12876-015-0340-0.
33. Lee H.O., Mullins S.R., Franco-Barraza J., Valianou M., Cukierman E., Cheng J.D. FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells // BMC Cancer. 2011. Vol. 11. P. 245. doi: 10.1186/1471-2407-11-245.
34. Liu C., Yu S., Zinn K., Wang J., Zhang L., Jia Y., Kappes J.C., Barnes S., Kimberly R.P., Grizzle W.E., Zhang H.G. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function // J. Immunol. 2006. Vol. 176 (3). P. 1375–1385.
35. Liu Y., Du L. Role of pancreatic stellate cells and periostin in pancreatic cancer progression // Tumour Biol. 2015. Vol. 36 (5). P. 3171–3177. doi: 10.1007/s13277-015-3386-2.
36. Masamune A., Shimosegawa T. Pancreatic stellate cells: A dynamic player of the intercellular communication in pancreatic cancer // Clin. Res. Hepatol. Gastroenterol. 2015. Vol. 39 (Suppl. 1). S. 98–103. doi: 10.1016/j. clinre.2015.05.018.
37. Mews P., Phillips P., Fahmy R., Korsten M., Pirola R., Wilson J., Apte M. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis // Gut. 2002. Vol. 50 (4). P. 535–541.
38. Mielgo A., Schmid M.C. Impact of tumour associated macrophages in pancreatic cancer // BMB Rep. 2013. Vol. 46 (3). P. 131–138.
39. Nakamura T., Mizuno S. The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine // Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2010. Vol. 86 (6). P. 588–610.
40. Neesse A., Algül H., Tuveson D.A., Gress T.M. Stromal biology and therapy in pancreatic cancer: a changing paradigm // Gut. 2015. Vol. 64 (9). P. 1476–1484. doi: 10.1136/gutjnl-2015-309304.
41. Neuzillet C., Tijeras-Raballand A., Cros J., Faivre S., Hammel P., Raymond E. Stromal expression of SPARC in pancreatic adenocarcinoma // Cancer Metastasis Rev. 2013. Vol. 32 (3–4). P. 585–602. doi: 10.1007/ s10555-013-9439-3.
42. Ninichuk V., Gross O., Reichel C., Khandoga A., Pawar R.D., Ciubar R., Segerer S., Belemezova E., Radomska E., Luckow B., Perez de Lema G., Murphy P.M., Gao J.L., Henger A., Kretzler M., Horuk R., Weber M., Krombach F., Schlöndorff D., Anders H.J. Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease // J. Am. Soc. Nephrol. 2005. Vol. 16 (4). P. 977–985.
43. Özdemir B.C., Pentcheva-Hoang T., Carstens J.L., Zheng X., Wu C.C., Simpson T.R., Laklai H., Sugimoto H., Kahlert C., Novitskiy S.V., De Jesus-Acosta A., Sharma P., Heidari P., Mahmood U., Chin L., Moses H.L., Weaver V.M., Maitra A., Allison J.P., LeBleu V.S., Kalluri R. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival // Cancer Cell. 2014. Vol. 25 (6). P. 719–734. doi: 10.1016/j.ccr.2014.04.005.
44. Pan B., Liao Q., Niu Z., Zhou L., Zhao Y. Cancer-associated fibroblasts in pancreatic adenocarcinoma // Future Oncol. 2015. Vol. 11 (18). P. 2603–2610. doi: 10.2217/FON.15.176.
45. Pang W., Su J., Wang Y., Feng H., Dai X., Yuan Y., Chen X., Yao W. Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts // Cancer Sci. 2015. Vol. 106 (10). P. 1362–1369. doi: 10.1111/cas.12747.
46. Qian L.W., Mizumoto K., Maehara N., Ohuchida K., Inadome N., Saimura M., Nagai E., Matsumoto K., Nakamura T., Tanaka M. Co-cultivation of pancreatic cancer cells with orthotopic tumor-derived fibroblasts: fibroblasts stimulate tumor cell invasion via HGF secretion whereas cancer cells exert a minor regulative effect on fibroblasts HGF production // Cancer Lett. 2003. Vol. 190 (1). P. 105–112.
47. Rhim A.D., Oberstein P.E., Thomas D.H., Mirek E.T., Palermo C.F., Sastra S.A., Dekleva E.N., Saunders T., Becerra C.P., Tattersall I.W., Westphalen C.B., Kitajewski J., Fernandez-Barrena M.G., Fernandez-Zapico M.E., Iacobuzio-Donahue C., Olive K.P., Stanger B.Z. Stromal elementsact to restrain, rather than support, pancreatic ductal adenocarcinoma // Cancer Cell. 2014. Vol. 25 (6). P. 735–747. doi: 10.1016/j.ccr.2014.04.021.
48. Rizwani W., Allen A.E., Trevino J.G. Hepatocyte growth factor from a clinical perspective: a pancreatic cancer challenge // Cancers (Basel). 2015. Vol. 7 (3). P. 1785–1805.
49. Rucki A.A., Zheng L. Pancreatic cancer stroma: Understanding biology leads to new therapeutic strategies // World J. Gastroenterol. 2014. Vol. 20 (9). P. 2237–2246. doi: 10.3748/wjg.v20.i9.2237.
50. Sato N., Maehara N., Goggins M. Gene expression profiling of tumor-stromal interactions between pancreatic cancer cells and stromal fibroblasts. Cancer Res. 2004. Vol. 64 (19). P. 6950–6956.
51. Schmid-Kotsas A., Gross H.J., Menke A., Weidenbach H., Adler G., Siech M., Beger H., Grünert A., Bachem M.G. Lipopolysaccharideactivated macrophages stimulate the synthesis of collagen type I and C-fibronectin in cultured pancreatic stellate cells // Am. J. Pathol. 1999. Vol. 155 (5). P. 1749–1758.
52. Sherman M.H., Yu R.T., Engle D.D., Ding N., Atkins A.R., Tiriac H., Collisson E.A., Connor F., Van Dyke T., Kozlov S., Martin P., Tseng T.W., Dawson D.W., Donahue T.R., Masamune A., Shimosegawa T., Apte M.V., Wilson J.S., Ng B., Lau S.L., Gunton J.E., Wahl G.M., Hunter T., Drebin J.A., O’Dwyer P.J., Liddle C., Tuveson D.A., Downes M., Evans R.M. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy // Cell. 2014. Vol. 159 (1). P. 80–93. doi: 10.1016/j.cell.2014.08.007.
53. Shi M., Yu D.H., Chen Y., Zhao C.Y., Zhang J., Liu Q.H., Ni C.R., Zhu M.H. Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its linicopathological significance // World J. Gastroenterol. 2012. Vol. 18 (8). P. 840–846. doi: 10.3748/wjg.v18.i8.840.
54. Sinn M., Sinn B.V., Striefler J.K., Lindner J.L., Stieler J.M., Lohneis P., Bischoff S., Bläker H., Pelzer U., Bahra M., Dietel M., Dörken B., Oettle H., Riess H., Denkert C. SPARC expression in resected pancreatic cancer patients treated with gemcitabine: results from the CONKO-001 study // Ann. Oncol. 2014 Vol. 25 (5). P. 1025–1032. doi: 10.1093/annonc/mdu084.
55. Sugimoto M., Mitsunaga S., Yoshikawa K., Kato Y., Gotohda N., Takahashi S., Konishi M., Ikeda M., Kojima M., Ochiai A., Kaneko H. Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas // Eur. J. Cancer. 2014. Vol. 50 (11). P. 1900–1908. doi: 10.1016/j.ejca.2014.04.010.
56. Tang Y., Xu X., Guo S., Zhang C., Tang Y., Tian Y., Ni B., Lu B., Wang H. An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma // PLoS One. 2014. Vol. 9 (3): e91551. doi: 10.1371/journal.pone.0091551.
57. Vonlaufen A., Joshi S., Qu C., Phillips P.A., Xu Z., Parker N.R., Toi C.S., Pirola R.C., Wilson J.S., Goldstein D., Apte M.V. Pancreatic stellate cells: partners in crime with pancreatic cancer cells // Cancer Res. 2008. Vol. 68 (7). P. 2085–2093. doi: 10.1158/0008-5472.CAN-07-2477.
58. Wang K., Tang J. Tumour-derived exosomes and their roles in cancer // Zhong Nan Da XueXueBao Yi Xue Ban. 2010. Vol. 35 (12). P. 1288–1292. doi: 10.3969/j.issn.1672-7347.2010.12.015.
59. Whatcott C.J., Diep CH, Jiang P, Watanabe A., LoBello J., Sima C., Hostetter G., Shepard H.M., Von Hoff D.D., Han H. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer // Clin.Cancer Res. 2015. Vol. 21 (15). P. 3561–3568. doi: 10.1158/1078-0432. CCR-14-1051.
60. Xu Z., Pothula S.P., Wilson J.S., Apte M.V. Pancreatic cancer and its stroma: A conspiracy theory // World J. Gastroenterol. 2014. Vol.20 (32). P. 11216–11229. doi: 10.3748/wjg.v20.i32.11216.
61.
Review
For citations:
Okladnikova E.V., Ruksha T.G. ROLE OF MICROENVIRONMENT IN THE DEVELOPMENT AND PROGRESSION OF PANCREATIC CANCER. Siberian journal of oncology. 2016;15(3):82-90. (In Russ.) https://doi.org/10.21294/1814-4861-2016-15-3-85-92
Views:
841
Email this article 
