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通过单链抗体片段M6-1B9胞内抗体降低EMMPRIN会影响α3β1整合素和MCT1的功能,并导致结肠癌细胞系Caco-2的进展性表型受到抑制。

EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2.

作者信息

Sangboonruang S, Thammasit P, Intasai N, Kasinrerk W, Tayapiwatana C, Tragoolpua K

机构信息

Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.

Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.

出版信息

Cancer Gene Ther. 2014 Jun;21(6):246-55. doi: 10.1038/cgt.2014.24. Epub 2014 Jun 13.

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN) exhibits overexpression in various cancers and promotes cancer progression and metastasis via the interaction with its associated molecules. The scFv-M6-1B9 intrabody has a potential ability to reduce EMMPRIN cell surface expression. However, the subsequent effect of scFv-M6-1B9 intrabody-mediated EMMPRIN abatement on its related molecules, α3β1-integrin, MCT1, MMP-2 and MMP-9, is undefined. Our results demonstrated that the scFv-M6-1B9 intrabody efficiently decreased α3β1-integrin cell surface expression levels. In addition, intracellular accumulation of MCT1 and lactate were increased. These results lead to suppression of features characteristic for tumor progression, including cell migration, proliferation and invasion, in a colorectal cancer cell line (Caco-2) although there was no difference in MMP expression. Thus, EMMPRIN represents an attractive target molecule for the disruption of cancer proliferation and metastasis. An scFv-M6-1B9 intrabody-based approach could be relevant for cancer gene therapy.

摘要

细胞外基质金属蛋白酶诱导剂(EMMPRIN)在多种癌症中呈过表达,并通过与其相关分子相互作用促进癌症进展和转移。单链抗体片段(scFv)-M6-1B9胞内抗体具有降低EMMPRIN细胞表面表达的潜在能力。然而,scFv-M6-1B9胞内抗体介导的EMMPRIN减少对其相关分子α3β1整合素、单羧酸转运蛋白1(MCT1)、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的后续影响尚不清楚。我们的结果表明,scFv-M6-1B9胞内抗体有效降低了α3β1整合素的细胞表面表达水平。此外,MCT1和乳酸的细胞内积累增加。这些结果导致结肠癌细胞系(Caco-2)中肿瘤进展特征(包括细胞迁移、增殖和侵袭)受到抑制,尽管MMP表达没有差异。因此,EMMPRIN是破坏癌症增殖和转移的一个有吸引力的靶分子。基于scFv-M6-1B9胞内抗体的方法可能与癌症基因治疗相关。

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