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The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells
Author(s) -
Ovalle Susana,
GutiérrezLópez María Dolores,
Olmo Nieves,
Turnay Javier,
Lizarbe María Antonia,
Majano Pedro,
MolinaJiménez Francisca,
LópezCabrera Manuel,
YáñezMó María,
SánchezMadrid Francisco,
Cabañas Carlos
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22902
Subject(s) - tetraspanin , carcinogenesis , integrin , cancer research , metastasis , cell growth , biology , ectopic expression , cell , cell adhesion molecule , cell adhesion , cancer , cell culture , immunology , biochemistry , genetics
The implication of the tetraspanin CD9 in cancer has received much recent attention and an inverse correlation between CD9 expression and the metastatic potential and cancer survival rate has been established for different tumor types. In contrast to the well‐established role of CD9 in metastasis, very little is known about the involvement of this tetraspanin in the process of development of primary tumors. In the present study, we present evidence on the implication of CD9 in colon carcinoma tumorigenesis. We report here that ectopic expression of CD9 in colon carcinoma cells results in enhanced integrin‐dependent adhesion and inhibition of cell growth. Consistently with these effects, treatment of these cells with anti‐CD9‐specific antibodies resulted in (i) increased β1 integrin‐mediated cell adhesion through a mechanism involving clustering of integrin molecules rather than altered affinity; (ii) induction of morphological changes characterized by the acquisition of an elongated cell phenotype; (iii) inhibition of cell proliferation with no significant effect on cell survival; (iv) increased expression of membrane TNF‐α, and finally (v) inhibition of the in vivo tumorigenic capacity in nude mice. In addition, through the use of selective blockers of TNF‐α, we have demonstrated that this cytokine partly mediates the antiproliferative effects of CD9. These results clearly establish for the first time a role for CD9 in the tumorigenic process. © 2007 Wiley‐Liss, Inc.