title: The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells.
abstract: 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.
authors.affiliation: Instituto de Farmacología y Toxicología (CSIC-UCM), Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Ovalle
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Gutiérrez-López
authors.forename: Nieves
authors.initials: N
authors.lastname: Olmo
authors.forename: Javier
authors.initials: J
authors.lastname: Turnay
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Lizarbe
authors.forename: Pedro
authors.initials: P
authors.lastname: Majano
authors.forename: Francisca
authors.initials: F
authors.lastname: Molina-Jiménez
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Cabrera
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Carlos
authors.initials: C
authors.lastname: Cabañas
mesh_terms: 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
chemical_list: 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