Hepatocyte growth factor (HGF) is involved in malignant behavior of cancers as a mediator of tumor-stromal interactions, facilitating tumor invasion and metastasis.
To examine the role of the HGF system in epithelial invasion followed by loss of connective tissue attachment in periodontitis, mRNA expression of HGF, its receptor (c-met) and HGFA in gingival tissues was monitored.
We also found that HGF upregulated the expression of IL-6 receptor mRNA in the same cell line, and that this upregulation enhanced the IL-6-induced cell invasion.
Met tyrosine kinase, the receptor for HGF/SF, is important in various cellular functions, including proliferation, mitogenesis, formation of branching tubules, angiogenesis, and tumor cell invasion and metastasis.
HGF stimulated the invasiveness of HepG2 cells in Matrigel cell invasion assay, together with increased expression of matrix metalloproteinase (MMP) 9.
Both in vitro (invasion and migration assays) and in vivo (murine tumour model) methods were used to ascertain the effect of NK4 on HGF/SF from two sources: human fibroblast-derived HGF/SF and recombinant HGF/SF.
Aberrant signalling through the hepatocyte growth factor/scatter factor receptor Met has been implicated in various aspects of the development of human cancer including the promotion of tumour invasion, angiogenesis and metastasis.
Cellular responses to invasion-stimulatory molecules such as scatter factor, chemokines, leptin, trefoil factors, and bile acids or inhibitory factors such as platelet activating factor and thrombin depend on activation of trimeric G proteins, phosphoinositide 3-kinase, and the Rac and Rho family of small GTPases.
These data show that hypoxia promotes tumor invasion by sensitizing cells to HGF stimulation, providing a molecular basis to explain Met overexpression in cancer.
Peritoneal dissemination is critical for the progression of ovarian cancer and our study revealed that HGF induces migration and invasion of ovarian cancer cells.
Expression of HGK mutants modulated integrin receptor expression and had a striking effect on hepatocyte growth factor-stimulated epithelial cell invasion.
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.
HGF activated Met signaling in all lines but elicited different responses: HGF induced cell dispersion (scattering) and collagen gel invasion in IOSE-Ov29 and IOSE-Ov29/T4 but did not alter the growth pattern of IOSE-29.
In these cells, we observe suppression of tumor cell growth and viability in vitro as well as inhibition of hepatocyte growth factor/scatter factor-mediated scattering and invasion in vitro, whether Met activation was ligand dependent or not.
To investigate the role of the HGF-Met system in these tumors, we examined HGF and Met expression in a variety of primary cultures, normal or malignant thyroid cells, and tissue specimens and analyzed the different HGF effects (promotion of mitogenesis, branching morphogenesis, and cell motility and invasion).
Consequently, HGF and BCL-2 family proteins use a furin-dependent pathway to promote invasion via TGF-beta and MMP in human malignant glioma cells and the pro-invasive properties of TGF-beta require furin- dependent MMP activity.
We identified two convergent proinvasive agents secreted by myofibroblasts: namely scatter factor/hepatocyte growth factor (SF/HGF) and the TGF-beta-upregulated extracellular matrix glycoprotein tenascin-C (TNC), each of which is necessary though not sufficient for invasion.
Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the cMET tyrosine kinase participate in cancer invasion, angiogenesis and metastasis in a wide variety of neoplastic cells.
In contrast, DU-145(+/+) cells had lost its response to HGF/SF induced invasion (22.33 +/- 2.08; P > 0.05 vs. control 23.5 +/- 2.11) and migration (24.12 +/- 0.86; P > 0.05 vs. control 23.27 +/- 0.81).
Finally, depletion of beta(4) by RNA interference in invasive carcinoma cells that express both receptors reduced the ability of these cells to invade toward HGF by approximately 25%, but it did not abrogate their invasion.