Suppressed collagen gene expression and induction of alpha 2 beta 1 integrin-type collagen receptor in tumorigenic derivatives of human osteogenic sarcoma (HOS) cell line.
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.
Santala
P
P
Department of Medical Biochemistry, University of Turku, Finland.
Larjava
H
H
Nissinen
L
L
Riikonen
T
T
Määttä
A
A
Heino
J
J
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002472:Cell Transformation, Viral; D003094:Collagen / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008745:Methylation; D008769:Methylnitronitrosoguanidine; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured
D016207:Cytokines; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D038981:Receptors, Collagen; D008769:Methylnitronitrosoguanidine; D003094:Collagen