A correlation between membrane cholesterol level, cell adhesion and tumourigenicity of polyoma virus transformed cells.
We have investigated the implications of the rise in membrane cholesterol levels on several in vitro and in vivo properties of polyoma virus transformed rat fibroblasts (PyF), with a special emphasis on alpha5beta1 integrin functions. We show that increased membrane cholesterol causes the PyF cells to change their shape and become more bipolar in appearance. These cells also show significantly higher adhesion to the cell-binding domain of fibronectin, increased localization of alpha5beta1 integrin and talin molecules in focal adhesions and a more robust actin cytoskeleton organization. PyF cells with increased membrane cholesterol show reduced growth in vitro and tumours caused by these cells in nude mice are slow growing. These changes in the growth properties of PyF cells are reversible when the cholesterol levels of PyF cells become normal. Our results suggest that changes in membrane cholesterol levels influence the growth and morphological properties of transformed cells, which can be exploited in controlling the growth of tumours in vivo.
Kaur
Tanvir
T
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Gopalakrishna
Praturi
P
Manogaran
Pulicat Subramanian
PS
Pande
Gopal
G
D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D002784:Cholesterol / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism; D011120:Polyomavirus / Q000378:metabolism*; D051381:Rats; D013050:Spectrometry, Fluorescence; D016608:Talin / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D000199:Actins; D004396:Coloring Agents; D005353:Fibronectins; D039081:Integrin alpha5beta1; D016023:Integrins; D016608:Talin; D013778:Tetrazolium Salts; D013844:Thiazoles; D002784:Cholesterol; C022616:thiazolyl blue