Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential
Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential
复制标题
口腔癌/内皮细胞融合经历核融合并获得增强的生存潜力
DOI：
10.1016/j.yexcr.2014.07.006
复制
发表时间：
2014
影响因子：
3.7
通讯作者：
Shang Zheng-jun
中科院分区：
文献类型：
--
作者：
Song Kai;Song Yong;Zhao Xiao-Ping;Shen Hui;Wang Meng;Yan Ting-lin;Liu Ke;Shang Zheng-jun
之前的大多数研究都将癌症-巨噬细胞融合与肿瘤进展和转移联系起来。然而，源自口腔癌和内皮细胞的杂交细胞的特征及其与癌症的关系仍然未知。采用免疫荧光双重染色和荧光原位杂交（FISH）证实eGFP标记的人脐静脉内皮细胞（HUVEC）与RFP标记的SCC9之间的自发细胞融合，并检测杂交体中vementin和细胞角蛋白18的表达。通过 TUNEL 测定检查了此类杂种的化学抗性特性。通过FISH和GFP/RFP双免疫荧光染色鉴定异种移植肿瘤中的杂交细胞。我们发现SCC9细胞自发地与共培养的内皮细胞融合，所得杂交细胞在重新铺板和解冻后仍保持分裂和增殖活性。与亲本 SCC9 细胞相比，此类杂交细胞表达两种亲本细胞的标记，并且对化疗药物顺铂更具抵抗力。我们的体内数据表明，根据 FACS 数据，即使杂交细胞和 SCC9 细胞以 1:10,000 的比例混合，通过使用免疫染色和 FISH 分析，杂交细胞仍有助于肿瘤组成。我们的研究表明，口腔癌和内皮细胞之间的融合事件发生核融合并获得新的耐药性，从而提高生存潜力。这些实验结果为细胞融合参与癌症进展的理论提供了进一步的支持证据。
Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression.