Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancer

Nagy, János; Curry, Graham; Hillan, Kenneth J.; McKay, I C; Mallon, Elizabeth; Purushotham, Arnie; George, W.D.

doi:10.1016/s0960-7404(96)80017-x

Cited by 50 publications

(32 citation statements)

References 31 publications

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“…In addition, Met is a tyrosine kinase implicated in breast cancer progression (42)(43)(44)(45)(46). Specifically, HGF/Met signaling pathways have been shown to increase tumor vasculature volume, promote local and distant invasion of tumor cells, and increase tumor growth and survival in mouse models (42,47,48). In human breast tumor samples, an average of 30% of samples express high levels of Met and 66% of samples express high levels of HGF in the primary tumor and/or the associated lymph node metastasis (44).…”

Section: Discussionmentioning

confidence: 99%

Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells

et al. 2008

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Breast cancers are not responsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), although 30% of breast cancers overexpress EGFR. The mechanism of intrinsic resistance to EGFR TKIs in breast cancer is the focus of current studies. Here, we observed that EGFR remains tyrosine phosphorylated in breast cancer cells that proliferate in the presence of EGFR TKIs. In one such cell line, SUM229, inhibiting c-Src kinase activity with either a dominantnegative c-Src or a c-Src TKI decreased EGFR phosphorylation on Tyr 845 , Tyr 992 , and Tyr 1086 in the presence of EGFR TKIs. Conversely, overexpressing wild-type (wt) c-Src in the EGFR TKI-sensitive breast cancer cell line SUM149 increased EGFR kinase-independent EGFR tyrosine phosphorylation. In addition, in the presence of EGFR TKIs, inhibiting c-Src kinase activity decreased cell growth in SUM229 cells, and overexpressing wt-c-Src increased cell growth in SUM149 cells. We identified the receptor tyrosine kinase Met to be responsible for activating c-Src in SUM229 cells. Inhibiting Met kinase activity with a small molecule inhibitor decreased c-Src phosphorylation and kinase activation. In addition, inhibiting Met kinase activity in SUM229 cells decreased EGFR tyrosine phosphorylation and growth in the presence of EGFR TKIs. Stimulating Met kinase activity in SUM149 cells with hepatocyte growth factor increased EGFR tyrosine phosphorylation and cell growth in the presence of EGFR TKIs. These data suggest a Met/c-Src-mediated signaling pathway as a mediator of EGFR tyrosine phosphorylation and cell growth in the presence of EGFR TKIs. [Cancer Res 2008;68(9):3314-22]

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Section: Discussionmentioning

confidence: 99%

Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells

et al. 2008

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“…In turn, these TAMs promote tumor cell proliferation by secreting a variety of tumor promoting factors, including nitric oxide (NO), EGF, FGF-8b, HGF/SF, IGF-I, TGF-b, VEGF-C and PDGF. Alternatively, activated macrophages can stimulate tumor cells to secrete these factors in an autocrine fashion [209][210][211][212][213][214]. Furthermore, TAMs themselves potently stimulate tumor angiogenesis and lymphangiogenesis by secreting growth factors, cytokines and chemokines [215][216][217].…”

Section: Tumor-associated Macrophagesmentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

209

160

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Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

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“…The Met RTK and its ligand, hepatocyte growth factor (HGF), are frequently overexpressed in breast cancer and correlate with decreased relapse-free and overall survival (15)(16)(17)(18)(19)(20). Indeed, Met receptor overexpression is an independent predictor of poor prognosis in breast cancer (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Met Receptor Contributes to Trastuzumab Resistance of Her2-Overexpressing Breast Cancer Cells

Shattuck

Miller

Carraway³

et al. 2008

Cancer Research

379

260

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Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancer

Cited by 50 publications

References 31 publications

Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells

Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Met Receptor Contributes to Trastuzumab Resistance of Her2-Overexpressing Breast Cancer Cells

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