Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin

What is it about?

In this study, we expose that conventional chemotherapies may paradoxically stimulate tumor growth and tumor recurrence after therapy. These therapies are designed to induce tumor cell death, however, we have shown that the resulting tumor cell debris can have potent pro-tumorigenic activity. One mechanism that contributes to this debris-stimulated phenomenon is through osteopontin, a well-characterized tumor-promoting factor. We show that the tumor cell debris stimulates residual tumor cells as well as macrophages to secreted dramatically higher levels of osteopontin. This elevated osteopontin then stimulates endothelial cell proliferation, suggesting that enhancing tumor angiogenesis is a mechanism by which osteopontin promotes tumor growth. Furthermore, we identify osteopontin as a therapeutic target for novel adjuvant therapies. For example, we observed that tumor-bearing mice treated with a combination of chemotherapy and osteopontin neutralizing antibody exhibited slowed tumor growth and regression compared to mice given either therapy alone. Taken together, our findings describe an underappreciated facet of chemotherapy as a double-edged sword, and also provide preclinical evidence suggesting that osteopontin is promising target for novel adjuvant cancer therapies.

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