Abstract
Abstract Lipid metabolism is supposed to be altered in breast cancer, and several literatures have suggested the possible compositional change of phospholipids in breast cancer tissues and its correlations with the tumor grade, sex hormone receptor status and patient's prognosis. However, the breast cancer cell-related alteration of phospholipid profiles and its underlying metabolic change remain unclear. The aim of this study is to investigate the cancer cell-related phospholipid alteration by using high resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). We evaluated the spatial distributions and the proportions of phosphatidylinositols (PIs) in seven breast cancer tissues (three luminal cases and four non-luminal cases including one Her2 positive case) and one normal breast tissue. MS images of PIs and their mass spectra showed that the fatty acyl chain compositions of observed PIs remarkably changed in cancer cell region, compared with those in normal duct epithelium or surrounding stromal cells. PIs containing polyunsaturated fatty acid (PUFA) were the major components in normal duct epithelium. In five of seven cancer cases, PIs containing monounsaturated fatty acid (MUFA) were the most dominant in the observed PIs and specifically upregulated in cancer cells. In the rest of the cases, the MUFA upregulation was less obvious than the aforementioned five cases, and PIs containing PUFA still constituted a large percentage of observed PIs. In non-luminal cases, the MUFA upregulation in cancer cells was well correlated with the expression level of stearoyl CoA desaturase 1 (SCD1), a key enzyme in de novo MUFA synthesis. This observation suggested that the upregulation of de novo MUFA synthesis in cancer cells could contribute to the increase of PIs containing MUFA. In conclusion, high resolution MALDI-IMS revealed the breast cancer cell-related changes of PI profiles according to the degree of the fatty acyl chain unsaturation, which implied the existence of cancer cell-related PI remodeling process. Citation Format: Masahiro Kawashima, Noriko Iwamoto, Nobuko Kawaguchi-Sakita, Masahiro Sugimoto, Takayuki Ueno, Kazuya Terasawa, Taka-Aki Sato, Koichi Tanaka, Kazuharu Shimizu, Masakazu Toi. High resolution imaging mass spectrometry reveals the breast cancer cell-related profiles of phosphatidylinositol unsaturation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3932. doi:10.1158/1538-7445.AM2013-3932
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