Accumulation of arachidonic acid-containing phosphatidylinositol at the outer edge of colorectal cancer.
Accumulation of arachidonic acid-containing phosphatidylinositol at the outer edge of colorectal cancer.
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DOI：
10.1038/srep29935
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发表时间：
2016-07-20
影响因子：
4.6
通讯作者：
Konno H
中科院分区：
文献类型：
--
作者：
Hiraide T;Ikegami K;Sakaguchi T;Morita Y;Hayasaka T;Masaki N;Waki M;Sugiyama E;Shinriki S;Takeda M;Shibasaki Y;Miyazaki S;Kikuchi H;Okuyama H;Inoue M;Setou M;Konno H
越来越多的证据表明，在包括结直肠癌在内的几种类型的癌症中，癌细胞显示出磷脂代谢的特异性改变，这有助于肿瘤的进展。至于哪些脂质是癌症组织外缘的特征，以及这些癌症外缘特异性脂质成分是否在癌细胞中自主出现，问题仍然存在。由纯原发癌细胞组成的癌组织起源球体（Cancer tissue- derived spheroid, cto）已经被开发出来。在这项研究中，我们旨在通过基质辅助激光解吸/电离(MALDI)-成像质谱（IMS）分析来自结直肠癌患者的ctos中的磷脂，寻找结直肠癌中癌细胞自主获取癌症外缘特征脂质。在负离子模式下，在表面区域检测到m/z 885.5的信号。经串联质谱分析，该信号为花生四烯酸(AA)-containing phosphatidylinositol (PI)， PI（18:0/20:4）。定量分析显示，cto表面的PI含量（18:0/20:4）比内侧高2倍。最后，PI（18:0/20:4）在结直肠癌患者的癌细胞/间质界面富集。这些数据暗示了含aa - PI在结直肠癌进展中的可能重要性，并提示表达含aa - PI的细胞是抗癌治疗的潜在靶点。
Accumulating evidence indicates that cancer cells show specific alterations in phospholipid metabolism that contribute to tumour progression in several types of cancer, including colorectal cancer. Questions still remain as to what lipids characterize the outer edge of cancer tissues and whether those cancer outer edge-specific lipid compositions emerge autonomously in cancer cells. Cancer tissue-originated spheroids (CTOSs) that are composed of pure primary cancer cells have been developed. In this study, we aimed to seek out the cancer cell-autonomous acquisition of cancer outer edge-characterizing lipids in colorectal cancer by analysing phospholipids in CTOSs derived from colorectal cancer patients with matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS). A signal at m/z 885.5 in negative ion mode was detected specifically at the surface regions. The signal was identified as an arachidonic acid (AA)-containing phosphatidylinositol (PI), PI(18:0/20:4), by tandem mass spectrometry analysis. Quantitative analysis revealed that the amount of PI(18:0/20:4) in the surface region of CTOSs was two-fold higher than that in the medial region. Finally, PI(18:0/20:4) was enriched at the cancer cells/stromal interface in colorectal cancer patients. These data imply a possible importance of AA-containing PI for colorectal cancer progression, and suggest cells expressing AA-containing PI as potential targets for anti-cancer therapy.