Laminin, the major non-collagenous component of the basement membrane, has been reported to increase the lnvasive and metastatic ability of tumour cells, to stimulate tumour cell growth adhesiveness to collagen type IV substrate, invasion through reconstituted basement membranes, in vivo metastic potential and in vitro collagenase activity, All this evidence suggests the possibility that the interaction of tumour cells with laminin may play a key role in the mechanism of tumour cells invasion. Aims of this project are:
A. To investigate the effect of laminin on the ability of invasive and metastatic carcinoma cell lines derived from patients with cancer of the oesophagus, ovary and pancreas to invade the extracellular matrix, focusing on its possible effect on the level of u-PA, one of the main proteases involvet in tumour invasion and degradation of the basement membrane.
B. To correlate the levels of u-PA, PAI-1 and/or u-PA receptor expressed by these cell lines with thelr invasive and degradative ability in vivo and in vitro, For this purpose in vitro invasion models (e.g. Matrigel) and experimental animals (e.g. n e mice, SCID-mice) will be employed.