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, 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 (67LR), a 31 kDa laminin binding protein with lectin binding properties (HLBP31), 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. Western immunoblot, immunohistochemistry, Northern blot, and in situ hybridization techniques are being used to assess specific expression in fixed and frozen tissues. 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. Preliminary evidence suggests that different types of cancer cells express specific laminin binding proteins, and that in breast cancers, 67LR and HLBP31 are inversely modulated. In cervical lesions, adenomatous cancers express more 67LR; however, squamous carcinomas to not differentially express this gene. In in vitro studies of steroid receptor-positive human breast cancer cell lines, 67LR appears to be upregulated by both estrogen and progesterone, while HLBP31 is responsive only to progesterone. These data demonstrate that estradiol and progestins differentially modulate the expression of genes involved in critical steps of cancer invasion and metastasis in human breast cancer cells.
