The expression of TGFbeta isoforms in primary and metastatic colon and breast cancer tissues has been shown to be upregulated in a number of studies while many cancer cells lose their sensitivity to TGFbeta growth inhibition due to mutation or down-regulation of the receptors. Some studies haver shown that enhanced TGFbeta expression can enhance tumorigenicity in vivo, perhaps by stimulating angiogenesis, inhibiting host immune response and altering cell adhesion and migration in a paracrine fashion. The type III receptor is the major TGFbeta receptor on cells and has been shown to be reduced in a number of breast and colon cancer cell lines. This investigator has also shown that expression of RIII by transfection in two breast tumor cell lines reduced their tumorigenicity in vitro or in vivo. The hypothesis to be tested is that RIII expression in breast and colon cancer cells can revert malignancy by antagonizing the paracrine tumor-promoting activity and perhaps enhancing autocrine tumor-suppressing activity of TGFbeta.
The specific aims are 1) determine the role of RIII in controlling the tumorigenicity of human breast and colon cancer cells, 2) determine whether RIII can suppress angiogenic potential of the cancer cells, 3) determine whether RIII expression can be employed in cancer immunotherapy, and 4) whether RIII expression can suppress the invasiveness and metastatic potential of the cancer cells.
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