Interaction of fibronectin with human colon adenocarcinoma cells: effect on the in vivo tumorigenic capacity.
Fibronectin (FN) modulates the behavior of the poorly differentiated, human colon adenocarcinoma-derived BCS-TC2 cells by promoting adhesion through the alpha(5)beta(1)-integrin, as this effect is blocked by anti-alpha(5) and beta(1 )chain antibodies. BCS-TC2 cells are not tumorigenic in vivo, but are able to form tumors when coinjected with FN in nude mice. From these tumors, a tumorigenic cell subline (BCS-TC2.FN) was established. In vivo passaging of BCS-TC2.FN cells in the absence of FN allowed the selection of another tumorigenic subline (BCS-TC2.FN2). The new sublines are characterized by: (1) increased differentiation, (2) slightly higher adhesion to FN, and (3) a higher uptake of [(3)H]thymidine, less dependent on the presence of serum or FN. No significant modifications in alpha(5)-chain surface levels were observed in the tumor-derived sublines, suggesting that the amount of alpha(5)beta(1)-integrin is not related to tumorigenicity. Within the heterogeneous parental cells, FN seems to favor the selection of a cell subpopulation that presents phenotypic and genotypic alterations that are stably maintained throughout in vitro culture and in vivo passaging. These cell lines constitute a model system that may help to extend our knowledge on the events underlying tumor progression and malignancy of colorectal cancer, and the influence of extracellular matrix components and their receptors in these processes.
Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad Complutense, Madrid, Spain.
M Teresa
MT
López-Conejo
Nieves
N
Olmo
Javier
J
Turnay
Isabel
I
López De Silanes
M Antonia
MA
Lizarbe
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D039482:Integrin alpha5; D007621:Karyotyping; D007797:Laminin / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D005353:Fibronectins; D039482:Integrin alpha5; D007797:Laminin; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D000469:Alkaline Phosphatase; D013936:Thymidine