Lipoptosis:: Tumor-specific cell death by antibody-induced intracellular lipid accumulation
Lipoptosis:: Tumor-specific cell death by antibody-induced intracellular lipid accumulation
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DOI：
10.1158/0008-5472.can-03-3149
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发表时间：
2004-06-01
期刊：
影响因子：
11.2
通讯作者：
Vollmers, HP
中科院分区：
文献类型：
--
作者：
Pohle, T;Brändlein, S;Vollmers, HP
平衡的脂质代谢对所有细胞都至关重要。由于脂肪酸的非生理性细胞内积累而扰乱这种稳态可导致细胞凋亡。这在动物研究中得到证实，并且与一些人类疾病相关，例如脂毒性心肌病。描述了脂肪细胞凋亡的一些代谢机制，并讨论了一些原因，但迄今为止尚未确定直接诱导脂肪细胞凋亡的试剂。利用传统的人杂交瘤技术（trioma技术）从胃癌患者中分离出人单克隆IgM抗体SAM-6。向肿瘤细胞添加SAM-6会导致细胞内中性脂质积累增加，随后肿瘤细胞凋亡。抗体 SAM-6 不会与非癌性人类上皮细胞和成纤维细胞发生反应，因为该抗体识别的 M-r 140,000 膜分子在人类恶性细胞上特异性表达。该抗体由种系基因 IgHV3-30.3*01 和 IgLV3-1*01 编码，是针对癌症的先天免疫的组成部分。在本文中，我们描述了一种抗体诱导的肿瘤特异性细胞死亡，称为脂肪凋亡。据我们所知，这是首次描述这种特定形式的脂肪细胞凋亡作为抗体介导的肿瘤细胞杀伤机制。
A balanced lipid metabolism is crucial for all cells. Disturbance of this homeostasis by nonphysiological intracellular accumulation of fatty acids can result in apoptosis. This was proven in animal studies and was correlated to some human diseases, like lipotoxic cardiomyopathy. Some metabolic mechanisms of lipo-apoptosis were described, and some causes were discussed, but reagents, which directly induce lipo-apoptosis, have thus far not been identified. The human monoclonal IgM antibody SAM-6 was isolated from a stomach cancer patient by using the conventional human hybridoma technology (trioma technique). The addition of SAM-6 to tumor cells leads to an increase in the intracellular accumulation of neutral lipids, followed by tumor cell apoptosis. The antibody SAM-6 does not react with noncancerous human epithelial and fibroblastic cells, because the M-r 140,000 membrane molecule, recognized by the antibody, is specifically expressed on human malignant cells. The antibody is coded by the germ-line genes IgHV3-30.3*01 and IgLV3-1*01 and is a component of the innate immunity to cancer. In this article, we describe an antibody-induced tumor-specific cell death, named lipoptosis. This is, to our knowledge, the first description of this specific form of lipo-apoptosis as an antibody-mediated mechanism of tumor cell killing.