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Query: UNIPROT:P14210 (hepatocyte growth factor)
 6,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Scatter factor (SF) is an invasogenic and angiogenic cytokine the cellular receptor of which is encoded by a proto-oncogene (c-met). We measured the immunoreactive SF content (nanograms of SF per milligram of protein) in tissue extracts from 166 breast cancers and correlated the values with various known prognostic parameters. Invasive cancers had nearly four times greater SF content than did ductal carcinoma in situ, and the difference was statistically significant (P < 0.02, two-tailed t-test). However, there were no significant differences in SF content among different histological types of invasive cancer. Invasive cancers that had spread to axillary lymph nodes exhibited higher SF content than did invasive cancers without regional spread (P < 0.02), but the difference in SF content between node-positive and node-negative tumors was not as great as that between invasive and ductal carcinoma in situ tumors. There was a trend toward increased SF content in larger primary tumors as compared with smaller tumors, but statistical comparison revealed borderline significance (0.05 < P < 1.0). There was no significant correlation between SF content and other parameters, including estrogen receptor, progesterone receptor, DNA ploidy, S phase, or Scarff-Bloom-Richardson score. We also measured the content of von Willebrand factor (a marker of blood vessels) and interleukin-1 beta (a pro-inflammatory cytokine) in the same tumor extracts. SF content showed a strong positive correlation with von Willebrand factor content (P < 0.001) but did not appear to be correlated with interleukin-1 beta. These findings suggest that SF is correlated with several other clinicopathological indicators of aggressive tumor behavior, consistent with the hypothesis that SF is a biological factor that may play a role in breast cancer pathogenesis.
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PMID:Scatter factor protein levels in human breast cancers: clinicopathological and biological correlations. 890 59

Genetic instability, alterations of tumor suppressor genes as well as activation of oncogenes and aberrant expression of growth factor/receptor system found in human stomach carcinogenesis are overviewed. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and amplification of the cyclin E gene are common events of both well differentiated and poorly differentiated gastric carcinomas. K-ras mutations, c-erbB2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC, LOH of the bcl-2 gene and LOH at DCC locus are preferentially associated with well differentiated gastric cancer. On the other hand, microsatellite instability, reduction or loss of cadherin and catenins, K-sam and c-met gene amplification confer the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cell-adhesion molecules in the c-met expressed cancer cells and hepatocyte growth factor from stromal cells is involved in morphogenesis of gastric cancer.
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PMID:[Multistep stomach carcinogenesis]. 892 Jun 75

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector for cells expressing the Met tyrosine kinase receptor. In this investigation, we show that pancreatic oval cells express Met and exhibit a proliferative response to HGF/SF. Additionally, we found that oval cells treated transiently with this factor become "scattered," whereas those exposed to HGF/ SF for extended periods of time form branching tubular structures. These structures possess true lumens, which are lined by cells with ductal features, including apical microvilli, well-developed intercellular junctions, interdigitation of plasma membranes, and abundant cytoplasmic organelles. Interestingly, these ductal structures are formed by HGF/SF-treated cells cultured on plastic dishes in the absence of exogenous extracellular matrix components. Consistent with their ability to form ductal structures in vitro, we found that pancreatic oval cells form ductal adenocarcinomas in nude mice. This study supports the involvement of HGF/SF-Met signaling in the growth, migration, and morphogenesis of pancreatic oval cells and may have important implications for the expansion and morphogenic differentiation of these cells during developmental, regenerative, and neoplastic growth.
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PMID:Hepatocyte growth factor/scatter factor-Met signaling induces proliferation, migration, and morphogenesis of pancreatic oval cells. 895 49

To investigate the roles of growth factors in bladder cancer, changes in the expression of messenger RNAs (mRNAs) for several growth factors and their receptors were examined during rat bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Northern blot analysis showed that the contents of mRNAs for transforming growth factor-alpha (TGF-alpha) and c-met/hepatocyte growth factor (HGF) receptor increased with BBN treatment. Epidermal growth factor (EGF) receptor mRNA was hardly affected by the treatment; while mRNA for fibroblast growth factor (FGF) receptor 1 and transforming growth factor-beta (TGF-beta) type II receptor decreased with BBN treatment. A rat bladder tumor cell line, NBT-II, expressed both TGF-alpha and c-met mRNAs, and HGF showed apparent scattering and growth-stimulating effects on the cells. These results indicate the possibility that TGF-alpha produced by a bladder cancer, in addition to urinary EGF, plays a role in the development of bladder cancer, and that enhanced cell motility due to activation of the c-met/HGF receptor participates in the invasion and metastasis of the cancer cells.
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PMID:Enhanced gene expression of transforming growth factor-alpha and c-met in rat urinary bladder cancer. 896 43

Scatter factor (SF, hepatocyte growth factor) is a cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. These responses are transduced through a tyrosine kinase receptor that is encoded by a proto-oncogene (c-met). SF is a potent angiogenic molecule, and its angiogenic activity is mediated, in part, through direct actions on endothelial cells. These include stimulation of cell motility, proliferation, protease production, invasion, and organization into capillary-like tubes. SF also stimulates the proliferation of smooth muscle cells and pericytes, cell types that also participate in the formation of capillaries and other microvessels. SF is chronically overexpressed in tumors, and it is postulated SF may function as a tumor angiogenesis factor. SF production in tumors may be due, in part, to an abnormal tumor: stroma interaction in which tumor cells secrete soluble proteins (SF-inducing factors) that stimulate stromal cell SF production and in part to autocrine production by the tumor cells themselves. Recent studies suggest a linkage between tumor suppressors (anti-oncogenes) and inhibition of angiogenesis. We hypothesize that tumor suppressor gene mutations may contribute to activation of an SF-->c-met signalling pathway, leading to an invasive and angiogenic tumor phenotype. Modulation of this pathway may provide clinically useful methods of enhancing or inhibiting angiogenesis.
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PMID:Regulation of angiogenesis by scatter factor. 900 33

Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.
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PMID:Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and neoplastic human liver tissue. 901 Apr 72

We have shown previously that hepatocyte growth factor (HGF), which is produced by lung fibroblasts, is a potent mitogen and motogen for both normal and neoplastic bronchial epithelium, and that expression of the HGF receptor, the c-met proto-oncogene protein, is uniformly found in the human bronchial epithelium and in non-small cell lung carcinomas (NSCLCs; P. Singh-Kaw et al., Am. J. Physiol., 268: L1012-L1020, 1995). Yamashita et al. have reported an association of HGF with poor survival in invasive ductal carcinoma of the breast (Cancer Res., 54: 1630-1633, 1994). There are few prognostic markers for lung cancer, and the high recurrence rate for stage I lung cancer suggests the frequent presence of undetectable tumor burden in such patients. Criteria are needed to evaluate these patients for risk of recurrence. We have now evaluated whether HGF present in resectable lung tumors has prognostic significance. In this study, 56 primary NSCLCs, mainly adenocarcinomas, were examined for presence of HGF by quantitative Western blot. These tumors consisted of tissue from 34 stage I patients, 9 stage II patients, and 13 stage IIIa patients who underwent curative resection for primary NSCLC. Extracts of whole tumor tissue were analyzed after separation of proteins by electrophoresis and transfer of proteins to nitrocellulose membranes. Immunoreactive (ir)-HGF was visualized by reaction with a polyclonal anti-HGF antiserum and quantitated by densitometry. Lung tumor content of ir-HGF varied widely among individuals. Median ir-HGF content in tumor extracts was 15.3 ng/40 microg of tumor protein; mean ir-HGF was 27.2 ng/40 microg of tumor protein. The median and mean ir-HGF were both significantly higher in tumor tissue from patients who suffered a recurrence during the follow-up period compared with those with no evidence or residual disease; this was true of all patients (P = 0.0001) and stage I patients analyzed separately (P = 0.002). Analysis of survival curves indicated that ir-HGF levels higher than the median were associated with poor overall survival (P < 0.03). Univariate analysis showed three factors related to poor overall survival in this set of patients: ir-HGF, tumor (T) status (a measure of primary tumor size and extent), and age. Nodal (N) status and stage were only marginally related to overall survival, most likely because the majority of the patients in the study were stage I. N status, stage, and T status were related to disease-free survival, however. Multivariate Cox analysis showed that ir-HGF, T status, and age independently had a negative impact on overall survival. ir-HGF was a strong independent negative prognostic indicator (P = 0.0001) with a relative risk of 1.022 per unit of ir-HGF (ng/40 microg of protein). This demonstrates that, in this group of patients, the relative risk of ir-HGF content increased continuously as ir-HGF increased, and exceeded 10 at units of ir-HGF of 100 or more. In comparison, in this group of patients, the relative risk of a T status greater than 1 was 4.75 and that of age greater than 65 was 3.95. The combined negative effect of a T status greater than 1 and elevated ir-HGF on survival was also highly pronounced (P < 0.005). In addition, elevated ir-HGF had a negative impact on survival when patients were stratified by stage or N status. Stage I patients with high ir-HGF values had a worse outcome than stage II or stage IIIa patients with low ir-HGF values. Elevated ir-HGF was strongly associated with poor outcome for resectable NSCLC patients as a group, and also identified stage I patients with poor outcome, indicating that it could be a useful indicator of risk of relapse and death in patients who have early lung cancer. The impact of elevated ir-HGF was especially prominent in patients whose T status was greater than 1, suggesting that patients with both risk factors who are stag
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PMID:Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. 901 70

Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived, multifunctional paracrine regulator possessing mitogenic, motogenic, and morphogenetic activities in cultured epithelial cells containing its tyrosine kinase receptor, Met. c-met has been implicated in oncogenesis through correlation of expression with malignant phenotype in specific cell lines and tumors. Paradoxically, however, HGF/SF can also inhibit the growth of some tumor cells. To elucidate the oncogenic role of HGF/SF in vivo, transgenic mice were created such that HGF/SF was inappropriately targeted to a variety of tissues. HGF/SF transgenic mice developed a remarkably broad array of histologically distinct tumors of both mesenchymal and epithelial origin. Many neoplasms arose from tissues exhibiting abnormal development, including the mammary gland, skeletal muscle, and melanocytes, suggesting a functional link between mechanisms regulating morphogenesis and those promoting tumorigenesis. Most neoplasms, especially melanomas, demonstrated overexpression of both the HGF/SF transgene and endogenous c-met, and had enhanced Met kinase activity, strongly suggesting that autocrine signaling broadly promotes tumorigenesis. Thus, subversion of normal mesenchymal-epithelial paracrine regulation through the forced misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent malignant transformation of cells of diverse origin.
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PMID:Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. 901 48

Fibroblasts have been considered to play an important role in tumor progression. In order to evaluate the contribution of fibroblasts to tumor invasion, TE2-NS, an esophageal cancer cell line, was cultured on collagen gel containing primary fibroblasts derived from normal esophageal submucosa or cancerous tissues of seven esophageal cancer patients. TE2-NS showed diverse invasiveness into the underlying gel containing fibroblasts, but did not invade the gel not containing fibroblasts. The invasiveness of TE2-NS, which expressed hepatocyte growth factor (HGF) receptor, was well-correlated with the concentration of HGF in conditioned medium. Administration of neutralizing antibody against HGF effectively suppressed the invasion, but application of recombinant HGF without fibroblasts induced little invasion into the gel. Fibroblasts from non-cancerous tissue generally secreted a larger amount of HGF and induced tumor invasion to a greater extent than those from cancer tissue, with large diversity. Interestingly, HGF secretion of fibroblasts from non-cancerous tissue was stimulated by co-culture with TE2-NS in two lines, but not in the other four. These results indicate that HGF is an important paracrine factor which induces tumor cell invasion, and the diversity of HGF production by fibroblasts might suggest different potentiality to induce tumor invasion among patients.
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PMID:Primary human fibroblasts induce diverse tumor invasiveness: involvement of HGF as an important paracrine factor. 904 42

The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). In this study, we examined HGF concentration and expression of the c-met proto-oncogene product (c-Met) in 62 patients with HCC to determine the relationship between the level of expression and clinicopathological features, and patient outcome following hepatectomy. Western blotting was used to examine the c-Met expression, and HGF concentration in tumors was measured using an enzyme-linked immunosorbent assay. c-Met was found to be overexpressed in HCC compared with nontumorous liver tissue (P < .01), and correlated with an increased incidence of intrahepatic metastases (P = .039). Patients were divided into two groups: low c-Met HCC and high c-Met HCC. Patients with high c-Met HCC had a significantly shorter 5-year survival than patients with low c-Met HCC (33.5% vs. 80.3%, respectively; P < .05). However, there was no correlation between HGF concentration in the tumor tissue and clinicopathological factors and patient survival. These results indicate that the expression of c-Met played an important role in tumor growth and metastases in patients who underwent hepatectomy for HCC.
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PMID:Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma. 904 8


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