Abstract
Cell-matrix interactions and intergrin-type cell adhesion receptors are involved in the regulation of tumor cell invasion and metastasis. We have analyzed the expression of matrix proteins and their cellular receptors in human osteosarcoma cells (HOS) and in their virally (KHOS-NP) and chemically (HOS-MNNG) transformed tumorigenic subclones. Transformation decreased dramatically the cellular mRNA levels of alpha 1(I) collagen. Concomitantly with down-regulation of collagen mRNA levels the synthesis of the collagen receptor, alpha 2 beta 1 integrin, was induced. No alpha 2 integrin mRNA was found in HOS cells, suggesting that its expression was regulated most probably at the transcriptional level. 5-Azacytidine alone or combined with alpha 2 integrin-stimulating cytokines, transforming growth factor-beta 1, and interleukin-1 beta, did not turn on the alpha 2 integrin gene. In chemically transformed cells, however, alpha 2 integrin expression could be regulated by cytokines. Thus, we suggest that HOS cells have a strong element, probably other than cell culture-generated de novo promoter methylation, suppressing alpha 2 integrin expression and that this factor is lost in both chemical and viral transformation. Furthermore, the mechanism used by cytokines and malignant transformation to increase alpha 2 integrin expression seems not to be identical. Other transformation-related changes in beta 1 integrins were (i) reduction of the intracellular pool of precursor beta 1 (in HOS-MNNG cells), leading to faster maturation rate of beta 1 subunit and slower maturation rate of alpha subunits, and (ii) decreased electrophoretic mobility of both alpha and beta 1 subunits. At the cellular level both chemical and viral transformation increased cell adhesion to type I collagen.
Highlights
Cell-matrix interactions and integrin-type cell adhe- Hynes (1992)). p l integrin can form a complex with at least sion receptors are involved in the regulation of tumor nine different a subunits, namely al-a8 and av
No a2 integrin mRNA was found in lymphocyte-homing receptor and a receptor for fibronectin, rec
The aim of this study was to analyze the putative changes in the cell-type I collagen interpellets obtained by centrifugation at 500 x g for 5 min were solubilized in 200 pl of the same buffer containing 100 m~ n-octyl p-D-glycopyranoside (Sigma)on ice with occasionalvortexing
Summary
Cell-matrix interactions and integrin-type cell adhe- Hynes (1992)). p l integrin can form a complex with at least sion receptors are involved in the regulation of tumor nine different a subunits, namely al-a8 and av. The abbreviations used are: HOS, human osteogenic sarcoma cells; FCS, fetal calf serum; IL, interleukin; TGF, transforming growth factor; MNNG, N-methyl-N"nitro-N-nitrosoguanidine;SCC, squamous cell carcinoma; GMK, green monkey kidney; DMEM, Dulbecco's modified quences of a2 and a3 integrin subunits (Fig. 1A).Their specificity was tested in immunoprecipitation assays. HOS-MNNG with other independent experiments done with fewer parallel cell lineisits chemically transformed,tumorigenicvariant samples.The expression level of a2 subunit was constantly
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