Involvement of TGF-Bs/TBRs system in tumor progression of murine mammary adenocarcinomas

CECILIA DAROQUI; LYDIA I. PURICELLI; ALEJANDRO J. URTREGER; PATRICIA ELIZALDE; GUILLERMO LANUZA; ELISA D. BAL DE KIER JOFFE

BREAST CANCER RESEARCH AND TREATMENT

SPRINGER

Lugar: Berlin; Año: 2003 vol. 80 p. 287 - 301

0167-6806

We studied the expression of TGF-b/TbR system and its biological role in tumor development, in M3 and MM3 murine mammary adenocarcinomas with different metastasizing capability and in LM3 and LMM3 derived cell lines. All the studied cells secreted TGF-bs and expressed TbRs. While the proliferation of the poorly metastatic M3 cells was significantly inhibited by 4 ng/ml TGF-bs, the highly metastatic MM3 cells were only slightly inhibited in response to the highest dose used. LM3 and LMM3 cells, highly invasive and metastatic, were totally refractory to TGF-b antiproliferative effect. The role of TGF-b in modulating key proteolytic cascades in tumor progression was also studied. TGF-bs enhanced metalloproteinases production in all the studied cells while induced a stimulatory net effect on plasmin system activity only in the more metastatic cells. Our results in this murine mammary tumor lineage support the concept that dissociation of TGF-b regulated growth control versus proteolytic enzyme pathways promotes tumor dissemination.