Abstract 2078: High-fat diet feeding increases the expression of chemokines in the target organs and their corresponding receptors in tumor tissues of mice injected with highly metastatic prostate cancer cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Prostate cancer is the third most common cancer in men worldwide. Recently, approximately 1 billion people in the world are overweight and obese, and epidemiological evidence indicates that overweight and obesity increase risks of developing several types of cancers. We previously noted that high-fat diet (HFD) feeding increased prostate cancer development and lung metastasis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. When TRAMP-C2 prostate cancer cells which were derived from a TRAMP mouse were subcutaneously injected into C57BL/6 mice, they grew in a solid tumor. However, distant metastasis was not detected. When these poorly metastatic TRAMP-C2 cells were injected into the tail vein, lung metastasis was detected at 15 weeks after the injection. In order to obtain highly metastatic clones, we isolated TRAM-C2 cells metastasized to the lung, cultured, injected again into the tail vein, and the process was repeated one more time. When the resulting highly metastatic cells (MTC2) were injected into the tail vein, metastasis was detected in the lung at 4.5 weeks. Compared to poorly metastatic TRAMP-C2, transcripts of the chemokine receptors CCR2 and CXCR2 were tremendously upregulated in highly metastatic MTC2. The ligands of these receptors, MCP-1 and CXCL1/CXCL2, stimulated the invasion of MTC2, and neutralizing antibodies against CCR2 and CXCR2 almost completely blocked the ligand-induced invasion indicating that these receptors are functional in MTC2. When MTC2 were injected into the tail vein, HFD-feeding stimulated lung metastasis. The transcripts of CXCL1 and CXCL2 were significantly increased in the lungs of HFD-fed mice. When MTC2 were subcutaneously injected into HFD-fed C57BL/6 mice, solid tumor growth and lymph node metastasis as well as tumor angiogenesis and lymphangiogenesis were significantly increased in HFD-fed mice. HFD feeding increased the transcripts of MCP-1, CXCL1, and CXCL2 in the lymph node as well as those of CXCR2 and CCR2 in tumor tissues. Additionally, the transcripts of CCR2, CCR7 and CXCR2 were increased markedly in MTC2 cells when co-cultured with mature adipocytes. In conclusion, we demonstrate that HFD-feeding accelerates the solid tumor growth, metastasis and lymphangiogenesis in C57BL/6 mice injected with prostate cancer cells. These results indicate that MCP-1, CXCL1, and CXCL2 in the metastatic target organs draw prostate tumor cells expressing their corresponding receptors. HFD feeding stimulates metastasis by not only increasing the levels of these ligands in the target organs but also increasing the levels of the receptors on tumor cells. Citation Format: Gyoo Taik Kwon, Hyerim Song,, Jung Han Yoon Park. High-fat diet feeding increases the expression of chemokines in the target organs and their corresponding receptors in tumor tissues of mice injected with highly metastatic prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2078. doi:10.1158/1538-7445.AM2014-2078