Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis

Webb, Craig P.; Taylor, Gregory A.; Jeffers, Michael; M, Fiscella; Oskarsson, M; Resau, James H.; Woude, GF Vande

doi:10.1038/sj.onc.1202135

Cited by 69 publications

(63 citation statements)

References 15 publications

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“…This HGF/SF-independent regulation of Met expression likely occurs through transcriptional activation via an AP-1 response element in the Met promoter. 35,60,68,69 In contrast, the HGF/SF dependent regulation of Met protein expression, on stimulation with exogenously added HGF/SF, is likely regulated by Met degradation via the ubiquitinylation pathway. 60 It is presently not known whether the amount of expressed Met receptor determines the responsiveness of benign or malignant prostate epithelial cells to HGF/SF stimulation in vivo.…”

Section: Discussionmentioning

confidence: 94%

“…As previously demonstrated, autocrine secretion of HGF/SF promotes metastases in a mouse model of tumor metastasis and HGF/SF plays a role in Ras-mediated metastases formation. 28,30,33,35 HGF/SF is an important mediator of stromal-epithelial interactions in the normal prostate; however, its specific function on Met-expressing epithelial cells has not been fully defined. 36 HGF/SF biological activity in the conditioned medium of mouse prostatic stromal cells, immortalized human myofibroblastic prostate stromal cells (PrSC), and primary PrSC stimulated the scattering, motility, and collagen gel invasion of DU145 prostate cancer cells and the proliferation of mouse prostate epithelial cells (PrEC).…”

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confidence: 99%

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Normal and Malignant Prostate Epithelial Cells Differ in Their Response to Hepatocyte Growth Factor/Scatter Factor

Gmyrek

Walburg

Webb

et al. 2001

The American Journal of Pathology

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Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF/SF is synthesized by prostate stromal cells (PrSCHepatocyte growth factor/scatter factor (HGF/SF) 1,2 has been implicated in the communication between stromal and epithelial cells of many different organs. HGF/SF is secreted predominantly by stromal cells and binds to its receptor, Met 3,4 mostly expressed on epithelial cells. Activation of the Met receptor tyrosine kinase affects a wide range of cellular processes, including growth and differentiation, morphogenesis and invasiveness. [5][6][7] The critical function of HGF/SF-Met in early development and during organogenesis is illustrated by the expression of Met in human embryonic tissues and by the identical phenotypes of HGF/SF and Met targeted knockout mice with early placental and hepatic defects. 8 -10 Gerald Cunha and collaborators 11,12 demonstrated the reciprocal nature of interactions between the stroma and epithelium in the determination of final organ structure. Several studies have suggested that mechanisms mediating the inductive interactions between the stroma and normal epithelium may also stimulate neoplastic cells during carcinogenesis and metastasis. 11,[13][14][15] This occurs through inappropriate expression or activation of receptors for stromal derived growth factors in tumor cells. 16 One of these receptors is Met which is aberrantly expressed or activated in a variety of human cancers. [17][18][19][20] Met was originally identified by its oncogenic potential in gene transfer experiments with DNA from transformed osteogenic sarcoma cells using the NIH 3T3 cell focus forming assay. 3 Dimerization of the cytoplasmic Met kinase activates its oncogenic function. 4,21 Constitutive Met activation is achieved through germline or somatic mutations in the Met kinase domain as detected in familial papillary renal cell carcinomas. 22,23 Transgenic expression of two independent strongly activating Met mutations as well as transgenic expression of tpr-met resulted in mammary carcinogenesis. 24,25 Furthermore, Met can be persistently activated through autocrine stimulation in tumor cells co-expressing Met and HGF/ SF. 26 -31 Based on the ability of HGF/SF to cause the dissociation of tumor cells from the primary tumor mass, to stimulate cell motility, and to elicit the activation of proteolytic cascades that degrade the extracellular matrix, 32-34 the HGF/SF-Met ligand-receptor system is a likely regulator of tumor metastases. As previously demonstrated, autocrine secretion of HGF/SF promotes metastases in a mouse model of tumor metastasis and Supported by Department of the Army grant DAMA-17-98-1-8592 (to B.S.K.).

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Normal and Malignant Prostate Epithelial Cells Differ in Their Response to Hepatocyte Growth Factor/Scatter Factor

Gmyrek

Walburg

Webb

et al. 2001

The American Journal of Pathology

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“…Tumor cell migration can be influenced by HGF and its receptor, Met. In Webb and coworkers' study (133), HGF and Met receptor signaling was associated with a transformed phenotype in rastransformed NIH 3T3 cells. Furthermore, the HGF pathway was recently reported to affect the adhesion and invasion of cancer cells (134).…”

Section: Growth Factor Receptor Pathways and Osteopontinmentioning

confidence: 99%

The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

Rodrigues

Teixeira

Schmitt

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

206

144

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The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1087 -97)

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“…We found that a locus (7q21) containing the MET gene was amplified in part of these EGFR wild-type tumors and immunohistochemically validated overexpression of MET protein in these tumors. MET was shown to be implicated in ras-mediated tumorigenicity (44,45) and activated in many tumors (34 -36). Although the number of cases with MET amplification is small in this study, it is tempting to speculate that amplification of the MET gene may play a role similar to EGFR mutation in lung adenocarcinoma.…”

Section: Imaging Diagnosis Prognosismentioning

confidence: 99%

Genetic Classification of Lung Adenocarcinoma Based on Array-Based Comparative Genomic Hybridization Analysis: Its Association with Clinicopathologic Features

Shibata¹,

Uryu

Kokubu³

et al. 2005

Clinical Cancer Research

100

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The array-based comparative genomic hybridization using microarrayed bacterial artificial chromosome clones allows high-resolution analysis of genome-wide copy number changes in tumors. To analyze the genetic alterations of primary lung adenocarcinoma in a high-throughput way, we used laser-capture microdissection of cancer cells and array comparative genomic hybridization focusing on 800 chromosomal loci containing cancer-related genes.We identified a large number of chromosomal numerical alterations, including frequent amplifications on 7p12, 11q13,12q14-15, and 17q21, and two homozygous deletions on 9p21 and one on 8p23. Unsupervised hierarchical clustering analysis of multiple alterations revealed three subgroups of lung adenocarcinoma that were characterized by the accumulation of distinct genetic alterations and associated with smoking history and gender. The mutation status of the epidermal growth factor receptor (EGFR) gene was significantly associated with specific genetic alterations and supervised clustering analysis based on EGFR gene mutations elucidated a subgroup including all EGFR gene mutated tumors, which showed significantly shorter disease-free survival. Our results suggest that there exist multiple molecular carcinogenesis pathways in lung adenocarcinoma that may associate with smoking habits and gender, and that genetic cancer profiling will reveal previously uncharacterized genetic heterogeneity of cancer and be beneficial in estimating patient prognosis and discovering novel cancer-related genes including therapeutic targets.

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Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis

Cited by 69 publications

References 15 publications

Normal and Malignant Prostate Epithelial Cells Differ in Their Response to Hepatocyte Growth Factor/Scatter Factor

Normal and Malignant Prostate Epithelial Cells Differ in Their Response to Hepatocyte Growth Factor/Scatter Factor

The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

Genetic Classification of Lung Adenocarcinoma Based on Array-Based Comparative Genomic Hybridization Analysis: Its Association with Clinicopathologic Features

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