Autophagic flux in cancer cells at the invasive front in the tumor-stroma border.
Autophagic flux in cancer cells at the invasive front in the tumor-stroma border.
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肿瘤-间质边界侵入前沿癌细胞的自噬流
DOI：
10.18632/aging.203406
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发表时间：
2021-08-17
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Yan F;Zhang X;Tan R;Li M;Xiao Z;Wang H;Zhang Z;Ma Z;Liu Z
在侵袭性前沿的癌细胞直接与基质组织相互作用，基质组织提供具有与肿瘤内组织不同的机械、营养和氧气供应特征的微环境。长期以来，人们已经知道，位于侵袭前沿的癌细胞和肿瘤体内的癌细胞表现出高度分化的功能和行为。然而，目前尚不清楚不同位置的癌细胞是否表现出各种自噬通量，这是一种重要的分解代谢过程，以维持细胞对环境变化的稳态。在这里，我们使用透射电子显微镜（TEM）发现，在人类原发性非小细胞肺癌（NSCLC）组织中，侵袭前沿的侵袭癌细胞（表现出间充质转录组特征）比瘤体内的癌细胞表现出更高的自噬通量。活细胞自噬通量监测系统结合3D器官型入侵共培养系统进一步证实了这种自噬特征。此外，自噬通量的增加赋予癌细胞侵袭行为，并与肿瘤分期的晚期和肺癌患者生存期的缩短正相关。这些发现扩展了对癌症侵袭过程中自噬动力学的理解。
Cancer cells at the invasive front directly interact with stromal tissue that provides a microenvironment with mechanical, nutrient, and oxygen supply characteristics distinct from those of intratumoral tissues. It has long been known that cancer cells at the invasive front and cancer cells inside the tumor body exhibit highly differentiated functions and behaviors. However, it is unknown whether cancer cells at different locations exhibit a variety of autophagic flux, an important catabolic process to maintain cellular homeostasis in response to environmental changes. Here, using transmission electron microscopy (TEM), we found that invading cancer cells at the invasive front, which show mesenchymal transcriptomic traits, exhibit higher autophagic flux than cancer cells inside the tumor body in human primary non-small cell lung cancer (NSCLC) tissues. This autophagic feature was further confirmed by a live cell autophagic flux monitoring system combined with a 3D organotypic invasion coculture system. Additionally, the increased autophagic flux endows cancer cells with invasive behavior and positively correlates with the advanced tumor stages and the reduced survival period of lung cancer patients. These findings expand the understanding of autophagic dynamics during cancer invasion.