Senescent tumor cells lead the collective invasion in thyroid cancer.
Senescent tumor cells lead the collective invasion in thyroid cancer.
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DOI：
10.1038/ncomms15208
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发表时间：
2017-05-10
影响因子：
16.6
通讯作者：
Park TJ
中科院分区：
文献类型：
--
作者：
Kim YH;Choi YW;Lee J;Soh EY;Kim JH;Park TJ
细胞衰老已被认为是一个障碍，对致癌作用。然而，衰老细胞的衰老相关分泌表型（SASP）可以促进肿瘤发生。在这里，我们发现衰老的肿瘤细胞经常出现在甲状腺乳头状癌（PTC）集体浸润的前部区域，以及淋巴管和淋巴结转移灶。在体外侵袭分析中，与非衰老肿瘤细胞相比，衰老肿瘤细胞通过SASP表达表现出高侵袭能力。PTC中的集体侵袭是由衰老肿瘤细胞引起的，其特征在于在前部区域产生C-X-C基序配体（CXCL）12趋化因子梯度。此外，衰老细胞通过CXCL 12/CXCR 4信号传导增加癌细胞的存活。原位异种移植体内模型也显示出与衰老细胞和癌细胞共移植的组中淋巴管参与更高。这些结果表明，衰老细胞积极参与PTC的集体侵袭和转移。衰老相关的基质细胞分泌表型可促进肿瘤发生。在这里，作者表明衰老癌细胞位于人乳头状甲状腺癌的侵袭前沿，并且衰老癌细胞通过CXCL 12在小鼠模型中驱动集体侵袭。
Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Here, we show senescent tumour cells are frequently present in the front region of collective invasion of papillary thyroid carcinoma (PTC), as well as lymphatic channels and metastatic foci of lymph nodes. In in vitro invasion analysis, senescent tumour cells exhibit high invasion ability as compared with non-senescent tumour cells through SASP expression. Collective invasion in PTC is led by senescent tumour cells characterized by generation of a C-X-C-motif ligand (CXCL)12 chemokine gradient in the front region. Furthermore, senescent cells increase the survival of cancer cells via CXCL12/CXCR4 signalling. An orthotopic xenograft in vivo model also shows higher lymphatic vessels involvement in the group co-transplanted with senescent cells and cancer cells. These findings suggest that senescent cells are actively involved in the collective invasion and metastasis of PTC. The senescence-associated secretory phenotype of stromal cells can promote tumorigenesis. Here, the authors show that senescent cancer cells are localized at the invasive front in human papillary thyroid carcinoma, and that senescent cancer cells drive collective invasion via CXCL12 in mouse models.