The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells.
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 beta1 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-alpha, and finally (v) inhibition of the in vivo tumorigenic capacity in nude mice. In addition, through the use of selective blockers of TNF-alpha, 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.
Ovalle
Susana
S
Instituto de Farmacología y Toxicología (CSIC-UCM), Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Gutiérrez-López
María Dolores
MD
Olmo
Nieves
N
Turnay
Javier
J
Lizarbe
María Antonia
MA
Majano
Pedro
P
Molina-Jiménez
Francisca
F
López-Cabrera
Manuel
M
Yáñez-Mó
María
M
Sánchez-Madrid
Francisco
F
Cabañas
Carlos
C
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D060245:Tetraspanin 29; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; D015703:Antigens, CD; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D016023:Integrins; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D014409:Tumor Necrosis Factor-alpha