State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Mol Cancer Ther. 2011 Dec;10(12):2276-86. doi: 10.1158/1535-7163.MCT-11-0487. Epub 2011 Oct 6.
The relapse and resistance to chemo- and radiotherapy are main problems in the treatment of human liposarcoma. It is important to find a functional marker existing in the liposarcoma cells for targeting. In this article, we established a new sub-cell line SW872-S cells with high tumorigenicity from human liposarcoma SW872 cells by repeated inoculation approach. The characteristic of the sub-cell line is linked to the high levels of integrin α6 on the surface. The integrin α6(high) cells show much higher tumor initiation and self-renewal potential in vivo than integrin α6(low) cells do. Targeting integrin α6 with its specific short interfering RNA and antibody significantly inhibits the cell adhesion to laminin and the tumor growth in vitro and in vivo, respectively. Interestingly, integrin α6 marks almost all of the surgical biopsy specimens of patients with liposarcoma relapse. Moreover, integrin α6 is found to coexpress with CD13, which might contribute to the antiapoptosis ability of integrin α6(high) cells. Consistently, integrin α6(high) cells are more sensitive to the CD13 inhibitor bestatin, and 61% of 23 other human tumor cell lines also contain integrin α6(high) CD13(high) subgroup. These results provide evidence, for the first time, to our knowledge, that integrin α6 and CD13 can serve as functional markers of the tumor-initiation subcell population in human liposarcoma as well as other cancers for therapeutic targeting.
化疗和放疗的复发和耐药是治疗人类脂肪肉瘤的主要问题。找到存在于脂肪肉瘤细胞中的功能标志物对于靶向治疗非常重要。在本文中，我们通过反复接种的方法从人脂肪肉瘤 SW872 细胞中建立了一个具有高致瘤性的新亚细胞系 SW872-S 细胞。该亚细胞系的特征与整合素α6在细胞表面的高表达有关。整合素α6（高）细胞在体内的肿瘤起始和自我更新能力明显高于整合素α6（低）细胞。用其特异性短发夹 RNA 和抗体靶向整合素α6，分别显著抑制细胞在体外和体内对层粘连蛋白的黏附和肿瘤生长。有趣的是，整合素α6几乎标记了所有脂肪肉瘤复发患者的手术活检标本。此外，整合素α6与 CD13 共表达，这可能有助于整合素α6（高）细胞的抗凋亡能力。一致地，整合素α6（高）细胞对 CD13 抑制剂 bestatin 更为敏感，23 种其他人类肿瘤细胞系中有 61%也含有整合素α6（高）CD13（高）亚群。这些结果首次提供证据表明，整合素α6和 CD13 可以作为人类脂肪肉瘤以及其他癌症的肿瘤起始亚群的功能标志物，用于治疗靶向。
