Amplification and overexpression of the met gene in spontaneously transformed NIH3T3 mouse fibroblasts.

Cooper, Christopher S.; Tempest, Philip R.; Beckman, M P; Heldin, Carl Henrik; Brookes, P.

doi:10.1002/j.1460-2075.1986.tb04543.x

Cited by 55 publications

(26 citation statements)

References 40 publications

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“…These in vitro results suggest that the c-METÐHGF/SF interaction promotes dissemination of lymphoma cells in vivo, like has been observed for transfected NIH3T3 cells and several epithelial cells (Cooper et al, 1986;Stoker et al, 1987;Iyer et al, 1989;Rong et al, 1992Rong et al, , 1993Rong et al, , 1994Liu et al, 1992;Giordano et al, 1993;Bellusci et al, 1994).…”

Section: Expression Of C-met Hgf/sf Production Cell Linessupporting

confidence: 64%

HGF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

et al. 1999

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The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF–c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 μg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly ( P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells ( P = 0.350 with Daudi cells and P = 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF–c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells. © 1999 Cancer Research Campaign

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Section: Expression Of C-met Hgf/sf Production Cell Linessupporting

confidence: 64%

HGF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

et al. 1999

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“…This is in line with the observations that HGF/SF has been found in blood and bone marrow plasma of leukemia patients 30,32 as well as in supernatants of human leukemia cell lines 31,42,43 and myeloma cells. 44 Transfection of the HGF/SF gene and/or c-MET gene in several epithelial cell lines and NIH3T3 cells [45][46][47][48][49][50][51][52] has revealed that these genes influence the invasiveness of these cells. Furthermore, studies for the expression pattern in normal, premalignant and malignant lesions has demonstrated overexpression of the c-MET gene in different tumors.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

et al. 1998

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Hepatocyte growth factor (HGF), also known as scatter factor (SF), is produced by mesenchymal cells, including bone marrow (BM) stromal cells, and has mitogenic and motogenic effects on a variety of cell types. Recently, a role has been assigned to HGF/SF and its receptor, c-MET, in both normal and malignant hemopoiesis. We investigated the function of HGF/SF on hemopoietic mononuclear cells (MNC) from patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with circulating blasts. In contrast to results with normal MNC, HGF/SF alone stimulated the proliferation and colony formation of MNC from these patients. MNC from some (4/13) of the AML patients also produced HGF/SF (0.1-0.2 ng/ml/day), while we could not detect HGF/SF in cultures from normal MNC. Furthermore, it appeared that HGF/SF induced migration of leukemic cells in Boyden using KG1a cells as a model for leukemic blasts. The membranes dividing the two compartments of the Boyden chambers were coated with fibronectin. HGF/SF significantly promoted migration in 3/5 samples of MDS patients and in 5/7 samples of AML patients. Supernatant of human BM stromal cells, which is chemoattractive for normal human hemopoietic progenitor cells, also promoted migration of MNC from 4/5 MDS patients and 6/7 AML patients. Since HGF/SF is one of the growth factors produced by BM stromal cells, a neutralizing antibody directed against HGF/SF was added to the BM stroma supernatant, which reduced migration significantly in 2/3 MDS and in 3/6 AML responders to BM stroma supernatant. In conclusion, HGF/SF promotes proliferation and migration of hemopoietic cells from AML and MDS patients in vitro and may therefore contribute to the malignant potential of these cells.

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“…Its activation involved a chromosomal rearrangement that linked tpr sequences on chromosome 1 with the tyrosine kinase domain of met on chromosome 7 (38). The met gene was shown to be amplified and overexpressed in spontaneous transformants of NIH 3T3 cells (8,21) and in human gastric carcinoma cell lines (16,26,41). The primary met proto-oncogene product is a 150-kDa precursor, which is glycosylated to generate a 170-kDa (p170"') protein.…”

mentioning

confidence: 99%

“…It was previously shown that spontaneous mouse NIH 3T3 cell tumors have amplified met sequences and that overexpression of the mouse met proto-oncogene (metmu) transforms NIH 3T3 cells (8,24). It was subsequently shown that fibroblast cells produce endogenous HGF/SF (49), suggesting that metmu transforms cells via an autocrine mechanism.…”

mentioning

confidence: 99%

Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor.

et al. 1992

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The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Methu) and mouse (Metmu) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrine activation mechanism for transformation by Metmu. However, the tumor-forming activity of Methu in NIH 3T3 cells is very low compared with that of Metmu, but efficient tumorigenesis occurs when Methu and HGF/SFhu are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Methu. The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SFhu expressed in NIH 3T3 cells produces tumors in nude mice.

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Amplification and overexpression of the met gene in spontaneously transformed NIH3T3 mouse fibroblasts.

Cited by 55 publications

References 40 publications

HGF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

HGF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells

Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor.

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