Obesity and Cancer: Biological Links and Treatment Implications.

Obesity is an epidemic disease and correlates with cardiovascular diseases increasing the overall mortality. However, it has been recently demonstrated that cancer is an unexpected consequence of obesity. In most of the studies, it is evaluated with body mass index (BMI): high BMI increases cancer risk and reduces survival of many solid tumors. The main biologic and clinic topics regarding obese cancer patients are here presented and discussed. Hyperinsulinemia and Insulin-like Growth Factors (IGFs) are among the most important links between cancer and obesity. However, adipose tissue (AT) also produces sex hormones, pro-inflammatory cytokines and hypoxia which in turn promote initiation and progression of tumors. One of the major clinic concern about obese cancer patients is the risk of chemotherapy-related toxicity. Previous studies showed that obese patients do not experience significant increased toxicity compared to non-obese patients. Thus, the increasing incidence and scientific knowledge of obesity should prompt the researchers to study for personalization of therapy in obese patients with cancer rather than for the simple chemotherapy "depotentiation". It has been demonstrated that weight loss reduces cancer risk and can ameliorate compliance to therapy. Thus, social politics as well as therapies against obesity may impact on cancer risk, treatment and survival.

Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells.

BACKGROUND: CXCR4, the chemokine receptor for CXCL12, has recently been involved in the metastatic process of several neoplasms. MATERIALS AND METHODS: The expression of CXCR4 was evaluated by immunohistochemistry of colorectal tissue samples and by flow cytometry on Caco2, GEO, SW480, SW48, Lovo and SW620 human colon carcinoma cell lines. Correlations with pathological characteristics of the specimens were analysed with chi-square test. To verify the functional status of CXCR4, cell lines were tested in adhesion, migration, and proliferation assays. RESULTS: We studied the expression of CXCR4 in 88 human colorectal tissues and we found that CXCR4 was expressed in > 10% of epithelial cells in 50% of normal mucosae (7/14), in 55% of polyps (29/53), in all of carcinomas (16/16) and hepatic metastasis (5/5). Notably, CXCR4 was significantly over-expressed in cancerous lesions (carcinomas and metastasis) compared to non-cancerous lesions (normal mucosa and polyps) (P = 0.003) and in adenomatous polyps versus hyperplastic polyps (P = 0.009). The diameter of a polyp was also significantly associated with CXCR4 expression (P = 0.031). SW480, SW48 and SW620 cell lines showed the highest levels of CXCR4 (60-80% of positive cells). Adhesion, migration, and proliferation increased in response to the CXCL12 chemokine. These effects were abrogated by the addition of anti-CXCR4 antibodies. Further, CXCL12 activated ERK1/2 in SW480 cells. CONCLUSIONS: These data suggest that CXCR4 might play a role in colon cancer cell properties and that anti-CXCR4 antibodies could have therapeutic effects against colorectal cancer.