Abstract 64: Differences in lipogenesis between cancer cells in culture and solid tumors

Abstract

Abstract Elevated lipogenesis is a characteristic feature of cancer. Fatty acid synthase (FASN) overexpression has been found in many human cancers. Tumor cells in culture and solid tumor models are essential tools to study cancer biology. A comparison of the models can reveal tumor microenvironmental influences on lipogenesis. Here we have characterized differences in lipid components such as total fatty acid (tFA) and phosphatidylcholine (PtCho) levels between tumor cells in culture and solid tumors, with 1H MR spectroscopy (MRS) of lipid-soluble cell or tumor extracts derived from breast and prostate cancer cell lines. MCF-12A, nonmalignant human mammalian epithelial cells, MDA-MB-231, an estrogen receptor (ER)/progesterone receptor (PR)-negative metastatic human breast cancer cell line and MCF-7, an ER/PR-positive poorly metastatic human breast cancer cell line, as well as PC-3 and DU-145, which are both androgen independent malignant human prostate cell lines were used in this study. Fully relaxed 1H MR spectra of lipid-soluble extracts from cells in culture and tumors were acquired on a Bruker Avance 500 MR spectrometer using tetramethylsilane (TMS) as an internal concentration standard. Total FA and PtCho levels were quantified as A.U./cell or A.U./g using integrals of the 1.3 ppm and 3.2 ppm signals in the 1H NMR spectra, respectively, normalized to the cell number or tumor weight (g). Patterns of PtCho and tFA levels were similar in cells, but different in tumors. Both PtCho and tFA levels were significantly higher in MCF-7 cells compared to MCF-12A and MDA-MB-231 cells. Interestingly, the levels of PtCho and tFA in nonmalignant MCF-12A cells and malignant MDA-MB-231 cells were comparable. However, the level of tFA in MDA-MB-231 tumors was significantly higher than in MCF-7 tumors. It has been known that hypoxia and low pH conditions activate FASN activity. FASN or/and other lipogenic enzymes in MDA-MB-231 tumors may be more sensitive to those microenvironmental factors. The tFA level of DU-145 cells was significantly higher compared with PC-3 cells. However, PtCho and tFA levels in PC-3 and DU-145 tumors were not significantly different. FASN protein levels in MCF-12A and MCF-7 cells were not significantly different. Since MCF-12A medium contains epidermal growth factor, which activates FASN, we need to further investigate the involvement of FASN without its activators and with only de novo fatty acid. Our results revealed that tFA levels of cells and tumors do not show similar patterns. The differences between cells and tumors can arise from environmental factors found in solid tumors such as depletion of nutrients and oxygen, changes in pH, as well as cancer cell and stromal/endothelial cell interactions. Additional studies are necessary to unravel the tumor microenvironmental factors responsible for the differences in lipid metabolism observed between cells grown in culture as compared to the same cells grown as solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 64.