Regulation of Anchorage-Independent Growth in Breast Cancer. Role of Signalling by Extracellular Matrix and Growth Factors.
Annual rept. 1 Aug 94-29 Jul 95,
QUEEN'S UNIV KINGSTON (ONTARIO)
Pagination or Media Count:
Anchorage-independent growth is a characteristic of transformed cells, however, we do not fully understand he mechanisms which allow cells to grow in the absence of adhesion and spreading. We have shown that partial depletion of fibronectin from serum reduces colony efficiency suggesting that fibronectin is required or colony growth. SPI cells express a number of B1 integrins on the cell surface, the most abundant being the ibronectin receptor a5B1. A monoclonal antibody to a5B1 BMA5 Inhibited adhesion to fibronectin by 90 colony growth of SPI cells is positively influenced by fibronectin and negatively by collagen type I. An SPI eII clone, Cl-12-ll, adhered well to collagen type I and expressed a2B1, and grows more efficiently in agar. n contrast the clone Cl-24-L did not adhere to collagen, express a2B1 or grow efficiently in agar. Cl-12-H cells grow more efficiently than Cl-24-L or SPI cells in serum free media. This growth can be inhibited by suramin, suggesting an autocrine loop. HGF receptor on SPI cells was not reduced under anchorage- dependent conditions, however, receptor phosphorylation was reduced but can be increased by addition of xogenous HGF.These results suggest that ECM-integrin interactions and growth factors are required for anchorage-independent growth of SPI cells.
- Medicine and Medical Research