Molecular studies on the role of cell-fibronectin interaction in tumourigenicity

Abstract

It is now well established that the interaction of cells with molecules of the newlineextracellular matrix can regulate various cell functions. Specifically, the newlineinteraction of cells with fibronectin (FN), plays an important role in this regard, newlineand therefore its regulation is of physiological significance. In principle, ceii-FN newlineinteractions can be regulated either (1) by altering levels of FN binding integrin newlinereceptors on the cell surface, or (2) by post translational modifications of the newlineintegrins involved. fn the present investigation, the mechanisms regulating the newlineinteraction of FN with the a5~ 1 integrin have been studied and their significance newlinein determining tumourigenic abilities of transformed cells and morphological newlinecharacteristics of normal mitotic cells has been examined. For this purpose three newlinecell systems have been used: (1) AK-5 tumour (2) polyoma virus transformed newlinefibroblasts (3) mitotic and interph.ase fibroblasts. newlineAK-5: a histiocytoma newlineAK-5 is an ascitic histiocytoma, consisting of four subpopulations (Band I - newlineBand IV cells) based on their bouyant density. The two major subpopulations newlinediffer markedly- Band I cells which are the lightest are more tumourigenic and newlinehave higher levels of cell surface FN than Band IV cells, which are the heaviest. newlineBand II and Ill cells are minor subpopulations with intermediate characteristics newline(Exp. Cell Res. 17 4, 41-48, 1988). In this study it has been found that Band I newlinecells have higher attachment ability to substrates coated with FN (4.0 times newlinemore) than Band IV cells. The differential ability to interact with FN is at least newlinepartly due to the higher levels (1.5 times more) of a 5 ~ 1 integrin on the cell newlinesurface of Band I cells than Band IV cells, as determined by flow cytometric newlineanalysis. The steady state mANA levels of the a 5 and ~ 1 subunits are also newlinecorrespondingly higher in Band I and Band IV cells. newline