Summary
Matrix metalloproteinase (MMP)-2 and -9 are secreted and translocated from endometrial stromal cells to cancer cells in a steroid-dependent manner. We investigated the paracrine effect of hepatocyte growth factor (HGF) on the expression of MMPs and tissue inhibitor of metalloproteinases (TIMPs) in stromal and endometrial cancer cells, and correlated the results with cancer cell invasiveness in a three-dimensional (3D) coculture. The 3D coculture of endometrial stromal and cancer cell lines (HEC-1A, HEC-IB, or KLE) was maintained in the presence or absence of HGF. Invasion of the cancer cells was quantified by Boyden’s chamber assay. Under the same conditions, the expression of MMP-2 and -9, membrane type-1 matrix metalloproteinase (MT1-MMP), and TIMP-1 and -2 were examined by zymography and reverse transcription-polymerase chain reaction. A significant increase in the invasiveness of all three cancer cells in the presence of HGF was observed by Boyden’s chamber assay. HGF enhanced the activation of MMP-2 and -9 by zymography of MMPs. HGF strongly induced MMP-9 mRNA expression in stromal cells, but had little effect on MMP-2 mRNA. MT1-MMP mRNA was detected only in KLE and stromal cells, and was also increased by the presence of HGF. TIMP-1 and -2 mRNAs were ubiquitous, with no dependence on HGF.
The effect of HGF on the invasiveness of 3D cocultured endometrial cancer cells and stromal cells appears to be due to: (1) the induction of MMP-9 mRNA expression in stromal cells; and/or (2) increased activation of MMP-2 and -9 by proteolytic digestion.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Liotta LA, Tryggvason K, Garbisa S et al. (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284:67–68
Barsky SH, Siegal GP, Jannotta F et al. (1983) Loss of basement membrane components by invasive tumors but not by their benign counterparts. Lab Invest 49:140–147
Yurchenco PD, Schittney JC (1990) Molecular architecture of basement membranes. FASEB J 4:1577–1590
Woessner JF Jr (1998) The matrix metalloproteinase family. In: Parks WC, Mecham RP (eds) Matrix metalloproteinases. Academic Press, San Diego, pp 1–14
Nelson AR, Fingleton B, Rothenberg ML et al. (2000) Matrix metalloproteinases: Biologie activity and clinical implications. J Clin Oncol 18:1135–1149
Karakiulakis G, Papanikolaou C, Jankovic SM et al. (1997) Increased type IV collagendegrading activity in metastases originating from primary tumors of the human colon. Invasion Metastasis 17:158–168
Park DW, Ryu HS, Choi DS et al. (2001) Localization of matrix metalloproteinases on endometrial cancer cell invasion in vitro. Gynecol Oncol 82:442–449
Nakamura T, Nishizawa T, Hagiya M et al. (1989) Molecular cloning and expression of human hepatocyte growth factor. Nature 342:440–443
Nakamura T, Nawa K, Ichihara A et al. (1987) Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett 224:311–318
Ponzetto C, Bardelli A, Zhen Z et al. (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77:261–271
Park M, Dean M, Kaul K et al. (1987) Sequence of Met protooncogene cDNA has features characteristic of the tyrosine kinase family of growth factor receptors. Proc Natl Acad Sci USA 84:6379–6383
Zhu H, Naujoskas MA, Fixman ED et al. (1994) Tyrosine 1356 in the carboxylterminal tail of the HGF/SF receptor is essential for the transduction of signals for cell motility and morphogenesis. J Biol Chem 269:29943–29948
Beviglia L, Kramer RH (1999) HGF induces FAK activation and integrin mediated adhesion in MTLn3 breast carcinoma cells. Int J Cancer 26:640–649
Matsumoto K, Matsumoto K, Nakamura T et al. (1994) Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal adhesion kinase (pl25FAK) and promotes migration and invasion by oral squamous cell carcinoma cells. J Biol Chem 269:31807–31813
Bae-Jump V, Segreti EM, Vandermolen D et al. (1999) Hepatocyte growth factor (HGF) induces invasion of endometrial cancer cell lines in vitro. Gynecol Oncol 73:265–272
Wang H, Keiser JA (2000) Hepatocyte growth factor enhances MMP activity in human endothelial cells. Biochem Biophys Res Commun 272:900–905
Cukierman E, Pankov R, Stevens DR et al. (2001) Taking cell-matrix adhesions to the third dimension. Science 294:1708–1712
Kuramoto H, Tamura S, Notake Y (1972) Establishment of a cell line of human endometrial adenocarcinoma in vitro. Am J Obstet Gynecol 15:1012–1019
McCawley LJ, O'Brien P, Hudson LG (1998) Epidermal growth factor (EGF)-and scatter factor/hepatocyte growth factor (SF/HGF)-mediated keratinocyte migration is coincident with induction of matrix metalloproteinase (MMP)-9. J Cell Physiol 176:255–265
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Nakamura T, Matsumoto K, Kiritoshi A et al. (1997) Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: In vitro analysis of tumor-stromal interactions. Cancer Res 57:3305–3313
Miyamori H, Hasegawa K, Kim KR et al. (2000) Expression of metastasis-associated mtsl gene is co-induced with membrane type-1 matrix metalloproteinase (MT1-MMP) during oncogenic transformation and tubular formation of Madin Darby canine kidney (MDCK) epithelial cells. Clin Exp Metastasis 18:51–56
Yoshida S, Harada T, Iwabe T et al. (2002) Induction of hepatocyte growth factor in stromal cells by tumor-derived basic fibroblast growth factor enhances tumor growth and invasion of endometrial cancer. J Clin Endocrinol Metab 87(5):2376–2383
Brooks PC, Strömbald S, Sanders LC et al. (1996) Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin αVβ3. Cell 85:683–693
Sato H, Seiki M (1996) Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. J Biochem 119:209–215
Knäuper V, Murphy G (1998) Membrane-type matrix metalloproteinases and cellsurface associated activation cascades for matrix metalloproteinases. In: Parks WC, Mecham RP (eds) Matrix metalloproteinases. Academic Press, San Diego, pp 199–218
Zucker S, Drews M, Conner C et al. (1998) Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1-matrix metalloproteinase 1 (MT1-MMP). J Biol Chem 273:1216–1222
Kinoshita T, Sato H, Okada A et al. (1998) TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix metalloproteinase immobilized on agarose beads. J Biol Chem 273:16098–16103
Hofmann A, Laue S, Rost AK et al. (1998) mRNA levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 and of their inhibitors TIMP-2 and TIMP-3 in normal thyrocytes and thyroid carcinoma cell lines. Thyroid 8:203–214
Knäuper V, Will H, Lopez-Otin C et al. (1996) Cellular mechanisms for human procollagenase-13 (MMP-13) activation: Evidence that MT1-MMP (MMP-14) and gelatinase A (MMP-2) are able to generate active enzyme. J Biol Chem 271:17124–17131
Collier E, Wilhelm SM, Eisen AZ et al. (1988) H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem 263:6579–6587
Pyke C, Ralfkiaer E, Huhtala P et al. (1992) Localization of messenger RNA for MR 72000 and 92000 type IV collagenases in human skin cancers by in situ hybridization. Cancer Res 52:1336–1341
Liu Y, Rajur K, Tolbert E et al. (2000) Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney Int 58:2028–2043
Hanzawa M, Shindoh M, Higashino F et al. (2000) Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes. Carcinogenesis 21:1079–1085
Haruyama T, Ajioka I, Akaike T et al. (2000) Regulation and significance of hepatocyte-derived matrix metalloproteinases in liver remodeling. Biochem Biophys Res Commun 272:681–686
Zambonin G, Camerino C, Greco G et al. (2000) Hydroxyapatite coated with hepatocyte growth factor (HGF) stimulates human osteoblasts in vitro. J Bone Joint Surg Br 82:457–460
Tamakoshi K, Kikkawa F, Nawa A et al. (1994) Different pattern of zymography between human gynecologic normal and malignant tissues. Am J Obstet Gynecol 171:478–484
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Japan
About this chapter
Cite this chapter
Ryu, HS., Choi, DS., Chang, KH., Park, DW., Min, C.K. (2003). Effect of Hepatocyte Growth Factor on the Expression of Matrix Metalloproteinases in the Invasion of Endometrial Cancer Cells in a Three-Dimensional Coculture System. In: Kuramoto, H., Nishida, M. (eds) Cell and Molecular Biology of Endometrial Carcinoma. Springer, Tokyo. https://doi.org/10.1007/978-4-431-53981-0_4
Download citation
DOI: https://doi.org/10.1007/978-4-431-53981-0_4
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67977-6
Online ISBN: 978-4-431-53981-0
eBook Packages: Springer Book Archive