OBJECTIVE: The association of transforming growth factor-beta 1 (TGF-beta 1) with a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase (TIMP), as well as myometrial invasion of endometrial cancer was studied. METHODS: The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity, and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancer patients with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta receptor Type I in tumor tissue from the same patients also was detected. RESULTS: Invasiveness, gelatinase activity, and the expression of TIMP-1 were higher in KLE cells than in Ishikawa cells, and they were increased by treatment with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1. The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage-Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were ubiquitous. CONCLUSIONS: Myometrial invasion of endometrial cancers involves an increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an autocrine or paracrine fashion.
OBJECTIVE: The association of transforming growth factor-beta 1 (TGF-beta 1) with a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase (TIMP), as well as myometrial invasion of endometrial cancer was studied. METHODS: The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity, and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancerpatients with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta receptor Type I in tumor tissue from the same patients also was detected. RESULTS: Invasiveness, gelatinase activity, and the expression of TIMP-1 were higher in KLE cells than in Ishikawa cells, and they were increased by treatment with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1. The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage-Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were ubiquitous. CONCLUSIONS: Myometrial invasion of endometrial cancers involves an increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an autocrine or paracrine fashion.
Authors: Jason Y Y Wong; Gordon S Huggins; Marcella Debidda; Nikhil C Munshi; Immaculata De Vivo Journal: Gynecol Oncol Date: 2008-04-18 Impact factor: 5.482
Authors: M Abal; M Llauradó; A Doll; M Monge; E Colas; M González; M Rigau; H Alazzouzi; S Demajo; J Castellví; A García; S Ramón y Cajal; J Xercavins; M H Vázquez-Levin; F Alameda; A Gil-Moreno; J Reventos Journal: Clin Transl Oncol Date: 2007-05 Impact factor: 3.405
Authors: Ran Xie; Matthew P Schlumbrecht; Gregory L Shipley; Susu Xie; Roland L Bassett; Russell R Broaddus Journal: Lab Invest Date: 2009-06-08 Impact factor: 5.662