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Autocrine and/or paracrine growth of aggressive ATLL cells caused by HGF and c-Met


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Title: Autocrine and/or paracrine growth of aggressive ATLL cells caused by HGF and c-Met
Authors: Onimaru, Yasuyuki / Tsukasaki, Kunihiro / Murata, K / Imaizumi, Yoshitaka / Choi, Y.L / Hasegawa, H / Sugahara, K / Yamada, Yasuo M A / Hayashi, T / Nakashima, M / Taguchi, T / Mano, Hiroyuki / Kamihira, Shimeru / Tomonaga, M
Issue Date: Oct-2008
Publisher: Spandidos Publications
Citation: International Journal of Oncology, 33(4), pp.697-703; 2008
Abstract: Adult T-cell leukemia/lymphoma (ATLL) is a neoplasia characterized by the massive invasion of various organs by tumor cells. Previously, we found that expression of the gene for c-Met, a receptor tyrosine kinase for hepatocyte growth factor (HGF), was specific to the acute type among 41 patients with ATLL by microarray. First in the present study, we analyzed the survival of the patients in relation to expression of c-Met and HGF in ATLL cells. Expression of the former but not the latter was associated with poor prognosis. Then, we analyzed the growth of ATLL cells caused by HGF and c-Met. c-Met was expressed in 0/7 chronic ATLLs, 12/14 acute ATLLs, 1/1 IL-2-independent ATLL cell line and 1/7 IL-2-dependent ATLL cell lines as assessed by flow cytometry. HGF induced the proliferation of primary cells from most acute cases examined as well as the c-Met-positive KK1 cell line in contrast to c-Met-negative cells. HGF induced autophosphorylation of c-Met in c-Met-positive cells from an acute case and KK1 cells. The plasma level of HGF was elevated in acute as compared to chronic cases. The levels of HGF and/or IL-6 which induces the production of HGF by stromal cells, were elevated in the supernatant of short-term cultured cells from certain patients with acute or chronic disease. Finally, infiltrated ATLL cells and adjacent stromal cells in liver were shown to be positive for c-Met/HGF and HGF, respectively, in acute cases. Autocrine and/or paracrine growth caused by HGF and c-Met was suggested in aggressive ATLL cells secreting HGF and/or IL-6, respectively.
Keywords: adult T-cell leukemia/lymphoma / human T-lymphotropic virus type-I / c-Met / hepatocyte growth factor / autocrine/paracrine
URI: http://hdl.handle.net/10069/22340
ISSN: 10196439
DOI: 10.3892/ijo_00000055
PubMed ID: 18813782
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22340

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