[Frontiers in Bioscience, Landmark, 20, 635-643, January 1, 2015]

HGF and c-Met in pathogenesis of endometrial carcinoma

Min Li 1 , Xiaoyan Xin 1 , Tingting Wu 1 , Teng Hua 1 , Hongbo Wang 1

1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. HGF and c-Met in endometrial stromal cells
4. HGF and c-Met in endometrial carcinoma
5. Downstream of HGF/c-Met signaling in endometrial carcinoma
6. Conclusions
7. References

1. ABSTRACT

Hepatocyte growth factor (HGF) regulates cell growth, motility, and morphogenesis of various types of cells via its receptor c-Met. In the growth of endometrium, HGF/c-Met signaling promotes the proliferation of both endometrial epithelial cells and stromal cells. In the onset and development of several cancers, HGF/c-Met signaling drives carcinogenesis and cancer invasion and metastasis. In endometrial carcinoma (EC), accounting for a majority of cancer-related morbidity and mortality among women, the increased expression of HGF and c-Met signaling is associated with a poor prognosis of EC patients. Thus, we will discuss the role of HGF and c-Met in the EC pathogenesis in this review.

7. REFERENCES

1. Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, Tashiro K, Shimizu S: Molecular cloning and expression of human hepatocyte growth factor. Nature 342(6248):440-3 (1989).
DOI: 10.1038/342440a0

2. Jiang W, Hiscox S, Matsumoto K, Nakamura T: Hepatocyte growth factor/scatter factor, its molecular, cellular and clinical implications in cancer. Crit Rev Oncol Hematol 29(3):209-48 (1999).
DOI: 10.1016/S1040-8428(98)00019-5

3. Morishita R, Aoki M, Yo Y, Ogihara T: Hepatocyte growth factor as cardiovascular hormone: role of HGF in the pathogenesis of cardiovascular disease. Endocr J 49(3):273-84 (2002).
DOI: 10.1507/endocrj.49.273

4. Sattler M, Salgia R: C-MET and hepatocyte growth factor: Potential new targets in cancer therapy. Curr Oncol Rep 9:102–108 (2007).
DOI: 10.1007/s11912-007-0005-4

5. Comoglio PM, Giordano S, Trusolino L: Drug development of MET inhibitors: Targeting oncogene addiction and expedience. Nat Rev Drug Discov 7:504–516 (2008).
DOI: 10.1038/nrd2530

6. Landi L, Minuti G, D’Incecco A, Cappuzzo F: Targeting c-MET in the battle against advanced non small-cell lung cancer. Curr Opin Oncol 25:130–136 (2013).
DOI: 10.1097/CCO.0b013e32835daf37

7. Yu S, Yu Y, Zhao N, Cui J, Li W, Liu T: C-Met as a prognostic marker in gastric cancer: A systematic review and meta-analysis. PLoS One 8:e79137 (2013).
DOI: 10.1371/journal.pone.0079137

8. Barrow-McGee R, Kermorgant S: Met endosomal signalling: In the right place, at the right time. Int J Biochem Cell Biol 49:69–74 (2014).
DOI: 10.1016/j.biocel.2014.01.009

9. Sheng XJ, Li Z, Sun M, Wang ZH, Zhou DM, Li JQ, Zhao Q, Sun XF, Liu QC: MACC1 induces metastasis in ovarian carcinoma by upregulating hepatocyte growth factor receptor c-MET. Oncol Lett 8(2):891-897 (2014).
Doi not found.

10. Pavan S, Musiani D, Torchiaro E, Migliardi G, Gai M, Di Cunto F, Erriquez J, Olivero M, Di Renzo MF: HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor. Int J Cancer 134(6):1289-99 (2014).
DOI: 10.1002/ijc.28464

11. Wang YC, Xu GL, Jia WD, Han SJ, Ren WH, Wang W, Liu WB, Zhang CH, Chen H: Estrogen suppresses metastasis in rat hepatocellular carcinoma through decreasing interleukin-6 and hepatocyte growth factor expression. Inflammation 35(1):143-9 (2012).
DOI: 10.1007/s10753-011-9299-3

12. Previdi S, Maroni P, Matteucci E, Broggini M, Bendinelli P, Desiderio MA: Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. Eur J Cancer 46(9):1679-91 (2010).
DOI: 10.1016/j.ejca.2010.02.036

13. Navab R, Liu J, Seiden-Long I, Shih W, Li M, Bandarchi B, Chen Y, Lau D, Zu YF, Cescon D, Zhu CQ, Organ S, Ibrahimov E, Ohanessian D, Tsao MS: Co-overexpression of Met and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells. Neoplasia 11(12):1292-300 (2009).
Doi not found.

14. Tsukinoki K, Yasuda M, Mori Y, Asano S, Naito H, Ota Y, Osamura RY, Watanabe Y: Hepatocyte growth factor and c-Met immunoreactivity are associated with metastasis in high grade salivary gland carcinoma. Oncol Rep 12(5):1017-21 (2004).
Doi not found.

15. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 61(2):69-90 (2011).
DOI: 10.3322/caac.20107

16. Wagatsuma S, Konno R, Sato S, Yajima A: Tumor angiogenesis, hepatocyte growth factor, and c-Met expression in endometrial carcinoma. Cancer 82(3):520-30 (1998).
DOI: 10.1002/(SICI)1097-0142(19980201)82:3<520::AID-CNCR14>3.0.CO;2-3

17. Bishop E A, Lengyel ER, Yamada SD, Montag A, Temkin SM: The expression of hepatocyte growth factor (HGF) and c-Met in uterine serous carcinoma. Gynecol Oncol 121(1):218-23 (2011).
DOI: 10.1016/j.ygyno.2010.11.031

18. Felix AS, Edwards RP, Stone RA, Chivukula M, Parwani AV, Bowser R, Linkov F, Weissfeld JL: Associations between hepatocyte growth factor, c-Met, and basic fibroblast growth factor and survival in endometrial cancer patients. Br J Cancer 106(12):2004-9 (2012).
DOI: 10.1038/bjc.2012.200

19. Bae-Jump V, Segreti EM, Vandermolen D, Kauma S: Hepatocyte growth factor (HGF) induces invasion of endometrial carcinoma cell lines in vitro. Gynecol Oncol 73(2):265-72 (1999).
DOI: 10.1006/gyno.1999.5353

20. Chan RW, Schwab KE, Gargett CE: Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 70(6):1738-50 (2004).
DOI: 10.1095/biolreprod.103.024109

21. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Matsuyama T, Ishimaru T: Estrogen and progesterone receptor expression in macrophages and regulation of hepatocyte growth factor by ovarian steroids in women with endometriosis. Hum Reprod 20(7):2004-13 (2005).
DOI: 10.1093/humrep/deh897

22. Tomica D, Ramiá S, Danoliá D, Knezeviá F, Kolak T, Balja MP, Alvir I, Mamiá I, Puljiz M: A correlation between the expression of estrogen receptors and progesterone receptors in cancer cells and in the myometrium and prognostic factors in endometrial cancer. Coll Antropol 38(1):129-34 (2014).
Doi not found.

23. Kreizman-Shefer H, Pricop J, Goldman S, Elmalah I, Shalev E: Distribution of estrogen and progesterone receptors isoforms in endometrial cancer. Diagn Pathol 9:77 (2014).
DOI: 10.1186/1746-1596-9-77

24. Zhang X: Hepatocyte growth factor system in the mouse uterus: variation across the estrous cycle and regulation by 17-beta-estradiol and progesterone. Biol Reprod 82(6):1037-48 (2010).
DOI: 10.1095/biolreprod.109.079772

25. Yoshida S, Harada T, Mitsunari M, Iwabe T, Sakamoto Y, Tsukihara S, Iba Y, Horie S, Terakawa N: Hepatocyte growth factor/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways. J Clin Endocrinol Metab 89(2):823-32 (2004).
DOI: 10.1210/jc.2003-030874

26. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Hiraki K, Sekine I, Matsuyama T, Ishimaru T: Interleukin-6- and tumour necrosis factor alpha-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis. Hum Reprod 20(10):2715-23 (2005).
DOI: 10.1093/humrep/dei156

27. Satterfield MC, Hayashi K, Song G, Black SG, Bazer FW, Spencer TE: Progesterone regulates FGF10, MET, IGFBP1, and IGFBP3 in the endometrium of the ovine uterus. Biol Reprod 79(6):1226-36 (2008).
DOI: 10.1095/biolreprod.108.071787

28. Khan KN, Kitajima M, Imamura T, Hiraki K, Fujishita A, Sekine I, Ishimaru T, Masuzaki H: Toll-like receptor 4-mediated growth of endometriosis by human heat-shock protein 70. Hum Reprod 23(10):2210-9 (2008).
DOI: 10.1093/humrep/den195

29. Hirata M, Sato T, Tsumagari M, Shimada A, Nakano H, Hashizume K, Ito A: Differential regulation of the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases by cytokines and growth factors in bovine endometrial stromal cells and trophoblast cell line BT-1 in vitro. Biol Reprod 68(4):1276-81 (2003).
DOI: 10.1095/biolreprod.102.006452

30. Guo W, Chen G, Zhu C, Wang H: Expression of matrix metalloproteinase-2, 9 and it’s tissue inhibitor-1, 2 in endometrial carcinoma. Zhonghua Fu Chan Ke Za Zhi 37(10):604-7 (2002).

31. Schlemmer SR, Kaufman DG: Endometrial stromal cells regulate gap-junction function in normal human endometrial epithelial cells but not in endometrial carcinoma cells. Mol Carcinog 28(2):70-5 (2000).
DOI: 10.1002/1098-2744(200006) 28:2<70::AID-MC2>3.0.CO;2-9

32. Chen C, Spencer TE, Bazer FW: Expression of hepatocyte growth factor and its receptor c-met in the ovine uterus. Biol Reprod 62(6):1844-50 (2000).
DOI: 10.1095/biolreprod62.6.1844

33. Fukaya T, Sugawara J, Yoshida H, Murakami T, Yajima A: Intercellular adhesion molecule-1 and hepatocyte growth factor in human endometriosis: original investigation and a review of literature. Gynecol Obstet Invest 47 Suppl 1:11-6; discussion 16-7 (1999).
DOI: 10.1159/000052854

34. Spencer TE, Bazer FW: Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Front Biosci 7:d1879-98 (2002).
Doi not found.

35. Murakami S, Miyamoto Y, Fujiwara C, Takeuchi S, Takahashi S, Okuda K: Expression and action of hepatocyte growth factor in bovine endometrial stromal and epithelial cells in vitro. Mol Reprod Dev 60(4):472-80 (2001).
DOI: 10.1002/mrd.1112

36. Dahabreh IJ, Schmid CH, Lau J, Varvarigou V, Murray S, Trikalinos TA: Genotype misclassification in genetic association studies of the rs1042522 TP53 (Arg72Pro) polymorphism: a systematic review of studies of breast, lung, colorectal, ovarian, and endometrial cancer. Am J Epidemiol 177(12):1317-25 (2013).
DOI: 10.1093/aje/kws394

37. Mrozikiewicz PM, Grześkowiak E, Seremak-Mrozikiewicz A, Bogacz A, Barlik M, Semczuk A, Bartkowiak-Wieczorek J, Drews K: Importance of CYP1A1 polymorphism and its transcriptional regulation in ovarian and endometrial cancer. Ginekol Pol 82(12):925-32 (2011).
Doi not found.

38. Zając A, Stachowiak G, Smolarz B, Wilczyński JR: Polymorphisms of codon 72 of the TP53 gene in endometrial carcinoma of postmenopausal women. Postepy Hig Med Dosw (Online) 67:1312-8 (2013).
DOI: 10.5604/17322693.1080804

39. Hosono S, Matsuo K, Ito H, Oze I, Hirose K, Watanabe M, Nakanishi T, Tajima K, Tanaka H: Polymorphisms in base excision repair genes are associated with endometrial cancer risk among postmenopausal Japanese women. Int J Gynecol Cancer 23(9):1561-8 (2013).
DOI: 10.1097/IGC.0b013e3182a80a7e

40. Liu Y, Michalopoulos GK, Zarnegar R: Structural and functional characterization of the mouse hepatocyte growth factor gene promoter. J Biol Chem 269(6):4152-60 (1994).
Doi not found.

41. Liu Y, Lin L, Zarnegar R: Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary. Mol Cell Endocrinol 1994;104(2):173-81 ().
DOI: 10.1016/0303-7207(94)90120-1

42. Moghul A, Lin L, Beedle A, Kanbour-Shakir A, DeFrances MC, Liu Y, Zarnegar R: Modulation of c-MET proto-oncogene (HGF receptor) mRNA abundance by cytokines and hormones: evidence for rapid decay of the 8 kb c-MET transcript. Oncogene 9(7):2045-52 (1994).
Doi not found.

43. Walentinsson A, Helou K, Wallenius V, Hedrich HJ, Szpirer C, Levan G: Independent amplification of two gene clusters on chromosome 4 in rat endometrial cancer: identification and molecular characterization. Cancer Res 61(22):8263-73 (2001).
Doi not found.

44. Arena S, Pisacane A, Mazzone M, Comoglio PM, Bardelli A: Genetic targeting of the kinase activity of the Met receptor in cancer cells. Proc Natl Acad Sci U S A 104(27):11412-7 (2007).
DOI: 10.1073/pnas.0703205104

45. Park YH, Ryu HS, Choi DS, Chang KH, Park DW, Min CK: Effects of hepatocyte growth factor on the expression of matrix metalloproteinases and their tissue inhibitors during the endometrial cancer invasion in a three-dimensional coculture. Int J Gynecol Cancer 13(1):53-60 (2003).
DOI: 10.1046/j.1525-1438.2003.13033.x

46. Yoshida S, Harada T, Iwabe T, Taniguchi F, Fujii A, Sakamoto Y, Yamauchi N, Shiota G, Terakawa N: Induction of hepatocyte growth factor in stromal cells by tumor-derived basic fibroblast growth factor enhances growth and invasion of endometrial cancer. J Clin Endocrinol Metab 87(5):2376-83 (2002).
DOI: 10.1210/jcem.87.5.8483

47. Choi DS, Kim HJ, Yoon JH, Yoo SC, Jo H, Lee SY, Min CK, Ryu HS: Endometrial cancer invasion depends on cancer-derived tumor necrosis factor-alpha and stromal derived hepatocyte growth factor. Int J Cancer 124(11):2528-38 (2009).
DOI: 10.1002/ijc.24238

48. Sundaram S, Le TL, Essaid L, Freemerman AJ, Huang MJ, Galanko JA, McNaughton KK, Bendt KM, Darr DB, Troester MA, Makowski L: Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression. Front Oncol 4:175 (2014).
DOI: 10.3389/fonc.2014.00175

49. Shi MD, Liao YC, Shih YW, Tsai LY: Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells. Phytomedicine 20(8-9):743-52 (2013).
DOI: 10.1016/j.phymed.2013.02.004

50. Kanayama S, Yamada Y, Kawaguchi R, Tsuji Y, Haruta S, Kobayashi H: Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells. Oncol Rep 19(1):117-22 (2008).
Doi not found.

51. Yoshizawa Y, Yamada Y, Kanayama S, Shigetomi H, Kawaguchi R, Yoshida S, Nagai A, Furukawa N, Oi H, Kobayashi H: Signaling pathway involved in cyclooxygenase-2 up-regulation by hepatocyte growth factor in endometrial cancer cells. Oncol Rep 26(4):957-64 (2011).
Doi not found.

52. Crouch S, Spidel CS, Lindsey JS: HGF and ligation of alphavbeta5 integrin induce a novel, cancer cell-specific gene expression required for cell scattering. Exp Cell Res 292(2):274-87 (2004).
DOI: 10.1016/j.yexcr.2003.09.016

53. Ho MY, Hung SW, Liang CM, Liang SM: Recombinant viral capsid protein VP1 suppresses lung cancer metastasis by inhibiting COX-2/PGE2 and MIG-7. Oncotarget 5(11):3931-43 (2014).
Doi not found.

54. Ho MY, Liang SM, Hung SW, Liang CM: MIG-7 controls COX-2/PGE2-mediated lung cancer metastasis. Cancer Res 73(1):439-49 (2013).
DOI: 10.1158/0008-5472.CAN-12-2220

Abbreviation: HGF: hepatocyte growth factor; EC: endometrial carcinoma; HGFA: HGF activator; IL-6: interleukin-6; TNF-alpha: tumor necrosis factor alpha; TIMP-2: metalloproteinase-2; MMP: matrix metalloproteina; ERE: estrogen responsive elements; MET-KD: kinase-inactive Met; PI3K: phosphatidylinositol 3-kinase; COX-2: cyclooxygenase-2

Key Words: HGF, endometrial carcinoma, TNF-alpha, TIMP-2, Review

Send correspondence to: Hongbo Wang, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan430022, China, Tel: 86 2785726301, Fax: 862785726301, E-mail: lm621113@yeah.net