Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation.

Rong, Sing; Segal, Shoshana; Anver, Miriam R.; Resau, James H.; Woude, George F. Vande

doi:10.1073/pnas.91.11.4731

Cited by 341 publications

(252 citation statements)

References 22 publications

Supporting

Mentioning

240

Contrasting

Order By: Relevance

“…It has been demonstrated that transformation of NIH3T3 cells through the expression of activated oncogenes, like Ras, Rho or Met, is accompanied by the acquisition of metastatic properties in athymic mice (Muschel et al, 1985;Rong et al, 1994;Del Peso et al, 1997). Here we show that oncogenic activation of Ron confers to NIH3T3 cells a metastatic phenotype.…”

Section: Discussionsupporting

confidence: 56%

Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the ron receptor

Santoro¹,

Penengo

Minetto

et al. 1998

Oncogene

View full text Add to dashboard Cite

Ron (the receptor for Macrophage Stimulating Protein) has never been implicated before in human malignancies or in cell transformation. In this report we show that Ron can acquire oncogenic potential by means of two amino acid substitutions ± D1232V and M1254T ± a ecting highly conserved residues in the tyrosine kinase domain. The same mutations in Kit and Ret have been found associated with two human malignancies, mastocytosis and Multiple Endocrine Neoplasia type 2B (MEN2B), respectively. Both mutations caused Ronmediated transformation of 3T3 ®broblasts and tumour formation in nude mice. Moreover, cells transformed by the oncogenic Ron mutants displayed high metastatic potential. The Ron mutant receptors were constitutively active and the catalytic e ciency of the mutated kinase was higher than that of wild-type Ron. Oncogenic Ron mutants enhanced activation of the Ras/MAPK cascade with respect to wild type Ron, without a ecting the JNK/SAPK pathway. Expression of Ron mutants in 3T3 ®broblasts led to di erent patterns of tyrosine-phosphorylated proteins. These data show that point mutations altering catalytic properties and possibly substrate speci®city of the Ron kinase may force cells toward tumorigenesis and metastasis.

show abstract

Section: Discussionsupporting

confidence: 56%

Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the ron receptor

Santoro¹,

Penengo

Minetto

et al. 1998

Oncogene

View full text Add to dashboard Cite

show abstract

“…The former mechanism is important in the generation of both inherited and spontaneous forms of papillary renal carcinoma , while the latter mechanism may be causative in a wide variety of malignant diseases, such as sarcomas (Rong et al, 1993a), carcinomas (Je ers et al, 1996c), melanomas (Saitoh et al, 1994), glioblastoma (Koochekpour et al, 1997;Laterra et al, 1997), and even multiple myeloma (Borset et al, 1996). Both mechanisms have been reproduced in cultured cells by stably transfecting cells with activated, mutant forms of Met (Je ers et al, 1997), or by co-transfecting Met and HGF/SF (Je ers et al, 1996a,b;Rong et al, 1994), thereby rendering the cells tumorigenic and capable of invasive growth and metastasis.…”

Section: Resultsmentioning

confidence: 99%

“…Promotion of metastasis by Met/HGF signaling (Rong et al, 1994) is thought to occur by increasing cell motility, angiogenesis (Grant et al, 1993), and the production of extracellular matrix proteases (Je ers et al, 1996b;Pepper et al, 1992). Modulation of extracellular glycoprotein production may be yet another means by which metastasis is promoted.…”

Section: Resultsmentioning

confidence: 99%

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

et al. 1998

View full text Add to dashboard Cite

The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor (HGF)/scatter factor are involved in the etiology and progression of a number of human cancers. Coexpression of Met and HGF in mesenchymal cells increases the tumorigenic and metastatic potential of the cells. In the studies described here, we used di erential display screening to identify changes in gene expression that are initiated by Met/HGF, and that may lead to these phenotypes. We learned that Met/ HGF signaling resulted in greatly decreased ®bronectin mRNA production in three di erent human and mouse tumor cell lines; these decreases in ®bronectin mRNA were paralleled by decreases in ®bronectin protein. We also found a progressive decrease in ®bronectin in tumor explants and metastases derived from the Met/HGF transformed cells. The absence of ®bronectin expression is a frequent cancer phenotype; our results indicate that decreases in ®bronectin correlate with, but are not essential for, MetHGF/SF-mediated tumorigenesis.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation.

Cited by 341 publications

References 22 publications

Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the ron receptor

Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the ron receptor

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

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

Contact Info

Product

Resources

About