Breast cancer metastasis is the leading cause of cancer deaths in women aged 45-65. Utilizing the rat 13762NF mammary adenocarcinoma tumor, we have developed an animal model for mammary carcinoma metastasis that closely mimicks human breast carcinoma. We have selected and double cloned variant tumor cell lines capable of spontaneous metastasis from mammary fat pad s.c. sites to regional lymph nodes and lung. We have determined the stabilities of these tumor clones and their propensities to undergo phenotypic drift in malignancy and tumor cell properties. We will now isolate and characterize cell surface glycoproteins from these cells which correlate with spontaneous metastasis and generate immunologic reagents against such glycoproteins. We will determine if differences in glycosaminoglycans, glycolipids or other components correlate with spontaneous metastasis using newly developed procedures. We will examine the adhesive properties of the tumor cell clones, including homotypic aggregation, platelet aggregation and interactions with newly isolated rat lung microvascular endothelial cells in vitro. These interactions will be blocked using specific monoclonal and polyclonal antibodies against cell surface components. We will also examine the tumor cell clones for specific degradative enzymes, in particular activities against various collagens, proteoglycans and glycoproteins. Finally, we will determine the sensitivities of the tumor cell clones to certain chemotherapeutic drugs in vitro and in vivo and primary and metastasic sites and develop a delivery system to preferentially treat established lung metastases.
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