One of the major challenges of cancer research is to define new methods for the detection of cancer lesions and to predict the aggressiveness and the metastatic potential of an individual patient's tumor. Such methods could help in the assessment of the best therapeutic strategy for a given patient. We have initiated a series of survey studies of breast, ovarian, endometrial, and cervical cancers to determine if specific genes are differentially expressed in those gynecological tumors that go on to metastasize. We are looking specifically at the expression of the 67 kDa high affinity laminin receptor, a 31 kDa laminin binding protein with lectin binding properties, as well as other genes that are thought to play a pathophysiological role in tumor cell invasion, including collagenases. Freshly frozen tumor samples and matched normal tissues are being analyzed at both the protein and RNA levels using specific antibodies and cDNA probes. Immunohistochemistry,Western immunoblot, Northern blot, and in situ hybridization techniques are being used to assess specific expression. Results will be correlated with the survival of cancer patients to establish the prognostic value of the systematic detection of these genes in gynecological tumors. As an adjunct to these survey studies, in vitro experiments are being conducted to determine the specific effect of steroid hormones on human breast cancer cells. Breast cancer cell lines derived from steroid receptor-negative tumors express higher levels of 67 kDa laminin receptor than do steroid receptor-positive cell lines. Steroid receptor-positive tumor cells that are grown in the presence of estrogen and progesterone increase their expression of laminin receptor up to the levels of steroid receptor-negative cell lines.
