Regulation of galectin-1 expression by transforming growth factor beta1 in metastatic mammary adenocarcinoma cells: implications for tumor-immune escape.
Tumors escape from immune surveillance by producing immunosuppressive cytokines and proapototic factors, including TGF-beta and galectin-1 (Gal-1). Since immunosuppressive mechanisms might act in concert to confer tumor-immune privilege, we investigated the potential cross talk between TGF-beta and Gal-1 in highly metastatic mammary adenocarcinoma (LM3) cells. While Gal-1 treatment was not capable of regulating TGF-beta synthesis, a pronounced and dose-dependent increase in Gal-1 expression was observed when tumor cells were treated with TGF-beta(1. )This effect was also observed in the murine lung adenocarcinoma LP07 and in the human breast adenocarcinoma MCF-7 cell lines. TGF-beta1-mediated upregulation of Gal-1 expression was specifically mediated by TbetaRI and TbetaRII, since it was abrogated when LM3 cells were infected with retroviral vectors expressing the dominant negative forms of these receptors. In addition, gal-1 gene sequence analysis revealed the presence of three putative binding sites for Smad4 and Smad3 transcription factors, consistent with the ability of TGF-beta(1) to trigger a Smad-dependent signaling pathway in these cells. Thus, TGF-beta(1) may trigger a Smad-dependent pathway to control Gal-1 expression, suggesting that distinct mechanisms might cooperate in tilting the balance toward an immunosuppressive environment at the tumor site.
Daroqui
Cecilia M
CM
Research Area, Institute of Oncology "Angel H. Roffo", University of Buenos Aires, San Martin Avenue 5481, Buenos Aires, Argentina.
Ilarregui
Juan M
JM
Rubinstein
Natalia
N
Salatino
Mariana
M
Toscano
Marta A
MA
Vazquez
Paula
P
Bakin
Andrei
A
Puricelli
Lydia
L
Bal de Kier Joffé
Elisa
E
Rabinovich
Gabriel A
GA
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D037483:Galectin 1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D020239:Receptor Cross-Talk / Q000276:immunology; D051785:Smad Proteins / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*; D019139:Tumor Escape / Q000502:physiology*
D037483:Galectin 1; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1