During the last year, the project has focused on the chemokine system in cancer. Chemokines and chemokine receptors can have roles in cancer by bringing white cells to the cancer and through direct effects on the cancer cells themselves. Although white cells can combat cancer by killing cancer cells, white cell products can also serve to enhance cancer cell growth, which is thought to be a mechanism whereby inflammation can promote cancer. Cancer cells that express chemokine receptors can also receive growth and/or survival signals from chemokines. In analyzing samples from human cancers that typically arise in association with inflammation, we have found that many of these cancers express the chemokine CXCL16. We concentrated on prostate cancer and using immunohistochemistry and immunofluorescence with confocal microscopy, we found that the cancer cells express both CXCL16 and CXCR6, and that high expression was associated with poor prognostic features. We also found expression by tumor-associated lymphocytes, and we hypothesize that both by bringing lymphocytes to the cancer and by directly stimulating cell growth, CXCL16 may be promoting prostate cancer. Another aspect of the project has explored using a second chemokine receptor, CXCR4, which is expressed on many cancers and is thought to be associated with aggressive cancer, in order to image cancers by positron emission tomography (PET). We have synthesized a radiolabeled CXCR4 antagonist, (64)Cu-AMD3100, that could potentially be used to identify CXCR4-expressing cancers and to correlate CXCR4 expression with prognosis and responses to therapy, thereby providing additional clinical information that might guide effective cancer therapy in individual patients.
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