[Loss of fibronectin receptor expression in malignant transformation of the colon results in increased tumorigenicity of epithelial cells].
Following malignant transformation, epithelial cells of colorectal carcinomas unlike normal colonic epithelial cells do not any longer express the classical alpha 5 beta 1 fibronectin receptor. We speculated that the loss of alpha 5 beta 1 expression may facilitate the tumorigenicity of transformed colonic cells. To examine this hypothesis, we established subclones of the human colon adenocarcinoma cell line HT29 which differ in their fibronectin receptor expression and tested their tumorigenicity in nude mice. Our data indicate that the capacity to form tumors in nude mice after subcutaneous injection was significantly lower for alpha 5 beta 1-positive than for alpha 5 beta 1-negative cell clones. In addition, tumors from clones expressing to detectable levels of alpha 5 beta 1 grew rapidly, while tumors expressing elevated levels of fibronectin receptor grew slowly. Deposition of fibronectin in tumor-surrounding stroma was increased in tumors derived from alpha 5 beta 1-positive cells compared to tumors derived from alpha 5 beta 1-negative cells. Our results indicate that a reduction of the alpha 5 beta 1-mediated interaction of epithelial cells with the extracellular matrix may be responsible for increased tumorigenicity of malignant transformed cells in colorectal carcinomas.
Stallmach
A
A
Medizinische Klinik und Poliklinik mit Schwerpunkt Gastroenterologie, Klinikum Steglitz, Freie Universität Berlin.
von Lampe
B
B
Orzechowski
H D
HD
Riecken
E O
EO
D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D017469:Receptors, Fibronectin / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000473:pathology*
D017469:Receptors, Fibronectin
Der Verlust der Fibronektinrezeptorexpression während der malignen Transformation im Kolon resultiert in einer gesteigerten Tumorigenität von Epithelzellen.