Summary: Breast and prostate cancer are usually lethal as a result of the spread/metastasis of tumor cells to distant organs in the body such as lung, liver, brain, and bone. Tumor progression and metastasis have been associated with high levels of inflammatory proteins, which are normally involved in wound healing and other immune responses.

Our lab studies the role of inflammatory proteins of the interleukin-6 (IL-6) family including oncostatin M (OSM) in tumor invasion and metastasis. Interesting data from our lab suggest that OSM induces the expression of many genes that promote the metastatic cascade, including vascular endothelial growth factor (VEGF), a potent proangiogenic factor, and the transcription factor hypoxia-inducible factor (HIF1). In addition, our lab was the first to show in vivo, using a mouse model of breast cancer, that OSM promotes tumor metastasis to bone, lung, and lymph nodes.

Our results provide the foundation for the rational design of cancer therapeutics that target OSM expression, function, or signaling. To date, there have been no attempts at inhibiting OSM for the purposes of cancer therapy.

Minimum Classes: Cell Biology (required) and Genetics (suggested).

Projects: Undergraduate and graduate students are currently involved in studies designed to determine the role of OSM in breast and prostate tumor progression and metastasis. I am looking for an INBRE undergraduate summer fellow who will work with us using prostate tumor cells to determine whether OSM promotes the expression of proteases such as MMPs (matrix metalloproteinases) and cathepsins, enzymes crucial for tumor cells to invade and metastasize. We believe that OSM-induced protease expression and function is highly relevant to the increased metastatic levels associated with OSM.

To contribute to this project, the student will: i) demonstrate that OSM induces protease expression by performing Western blot analysis on prostate cancer cell lysates from cells treated with or without OSM, and ii) determine whether OSM-induced proteases are functionally active by performing Zymography assays. These findings will improve our understanding of the role that OSM plays in tumor progression and metastasis.

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