Prostaglandin E?2? (PGE?2?) is secreted in high concentrations by a variety of human and animal tumors including the murine Lewis lung carcinoma (LLC). The goal of this study is to determine if PGE?2? could promote tumor metastasis by directly influencing the ability of malignant cells to disseminate from the primary neoplasm to distant sites. Malignant and non-metastatic LLC variants will be isolated and cloned. A radioimmunoassay for quantitating PGE?2? will be used to determine if malignant cells produce more PGE?2? than cells not capable of metastasizing. The in vivo metastatic potentials of the LLC clones will be correlated with their ability to migrate in an in vitro model for the early stages of metastasis: dissemination of malignant cells from a primary neoplasm. With this model, the role of PGE?2? in influencing the migration and presumably the metastatic properties of the tumor cells can be studied in the absence of immune interference in tumor cell survival. The modulation of the malignant properties of cells by PGE?2? will be confirmed in vivo. The results of this study are expected to determine if PGE?2? produced by LLC could promote the early stages of the metastatic process. (M)
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