In vitro exposure of polyoma-virus-transformed cells to laminin augments their in vivo malignancy phenotype.
The aim of this study was to assess the influence of the extracellular matrix (ECM) proteins laminin and fibronectin on the malignancy phenotype of BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV). The in vitro incubation of low-tumorigenicity cells from a PyV-transformed clone on laminin-coated plates, and to a lesser extent on fibronectin-coated ones, increased their ability to form experimental metastases as well as local tumors. The in vitro exposure of PyV-transformed cells to laminin was also accompanied by a downregulation of the membrane NI/32.2 antigen which is a PyV-associated tumor antigen. Downregulated expression of this antigen has been previously shown to be associated with the progression of PyV-transformed cells from a low- to a high-tumorigenicity phenotype. The in vitro exposure of the PyV-transformed cells to the ECM proteins did not affect several other phenotypic characteristics associated with high malignancy such as doubling time and resistance to killing mediated by tumor necrosis factor-alpha. The ability of the laminin- or fibronectin-treated cells to bind laminin was identical to that of control cells. While not excluding the possibility that the laminin-mediated augmentation of tumorigenicity and metastasis may be a result of in vitro selection of high tumorigenicity variants expressing high laminin binding, the possibility exists that laminin may control the expression of genes associated with the progression of PyV-transformed cells.
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
B Z
BZ
Katz
I P
IP
Witz
D016475:3T3 Cells; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000209:etiology*; D010641:Phenotype; D011120:Polyomavirus
D005353:Fibronectins; D007797:Laminin