ODP548 Fatty acid metabolism-related factors in breast and endometrial cancers

Abstract

Abstract Obesity is a well-known risk factor for gynecological malignant tumors such as breast and endometrial cancers. In the cancer microenvironment, the interaction between cancer cells and adipocytes reportedly contributes to the malignant behavior of cancer. In breast cancer, the fatty acid transporter CD36, also known as fatty acid translocase, has been shown to mediate fatty acid uptake into cancer cells and activate signaling pathways that promote tumor progression. Fatty acids are speculated to play important roles in breast and endometrial cancer; however, detailed mechanisms remain unclear. In the present study, we first examined the expression of CD36 and acyl-CoA dehydrogenase long chain (ACADL) in breast (30 cases) and endometrial (35 cases) cancer tissues using immunohistochemistry. CD36 is a membrane protein that transports long-chain fatty acids, and ACADL catalyzes the initial β-oxidation reaction. We detected no correlation between the CD36 status and clinicopathological factors, including the estrogen receptor status in breast cancer tissues. CD36 status revealed a significant positive correlation with lymph node metastasis in endometrial cancer. There was no immunoreactivity for CD36 in morphologically normal mammary glands. Otherwise, CD36 immunoreactivity was detected in the endometrial glandular cells. In both cancers, ACADL expression did not correlate with any clinicopathological factor. Both CD36 and ACADL showed higher positivity rates in endometrial cancer than in breast cancer. In addition, the effect of lipid addition on cell proliferation was examined using breast (T-47D) and endometrial (AN3CA) cancer cell lines exhibiting equivalent CD36 levels. Lipid (Refeed JNS) was obtained from Remembrane, Italy. Lipid addition promoted cell proliferation in both T-47D and AN3CA cells. Intracellular fatty acid β-oxidation (FAO) was visualized using FAOBlue (Funakoshi, Tokyo, Japan), a nonanoic acid (C9) derivative of coumarin, a blue fluorescence dye. Following FAOBlue decomposition in the fourth FAO cycle, coumarin is released from propionic acid, and released coumarin shows strong blue fluorescence excited at 405 nm. T-47D cells showed blue fluorescence in the lipid-supplemented medium, indicating β-oxidative activity. Conversely, AN3CA cells exhibited weak fluorescence under the same conditions. It can be postulated that intracellular lipid uptake and subsequent β-oxidation are mediated via a specific pathway in breast and endometrial cancers. Lipid-mediated effects differ between breast and endometrial cancers, and further investigations are needed to elucidate intracellular signals mediating these effects. Presentation: No date and time listed