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首页> 外文期刊>Cell cycle >Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam? histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.
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Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam? histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.

机译：癌细胞模拟3维Gelfoam中的体内时空细胞周期相分布和化学敏感性。组织培养，而不是实时FUCCI成像可视化的二维培养。

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摘要

The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam? collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam? and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam? culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam? culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.
机译：细胞周期的阶段可以确定癌细胞是否可以对给定的药物产生反应。我们之前报道过，使用基于荧光泛素化的细胞周期指示剂（FUCCI）监测活小鼠体内的整个活肿瘤中癌细胞的实时细胞周期动态。在已建立的肿瘤中心，大约90％的癌细胞和80％的总细胞处于G0 / G1期。纵向实时成像表明，细胞毒剂仅杀死表面增殖的癌细胞，相反，对静止的癌细胞几乎没有影响，而静止的癌细胞是已建立的肿瘤的绝大部分。而且，抗药性的静态癌细胞在停止化疗后重新开始循环。这些结果表明为什么目前临床上使用的大多数靶向S / G2 / M癌细胞的药物对实体瘤大多无效。在本报告中，我们使用了FUCCI成像和Gelfoam？胶原海绵凝胶组织培养法可实时显示，明胶泡沫中癌细胞的细胞周期相分布？与体内肿瘤高度相似，因此在G0 / G1中仅表面细胞增殖而内部细胞处于静止状态。这与大多数癌细胞循环的2D培养相反。同样，癌细胞对Gelfoam？的毒性化疗反应相似。癌细胞在体内的培养与化学敏感性大不相同。明胶泡沫？表达FUCCI的癌细胞的培养提供了连续成像癌细胞的细胞周期和筛选靶向静止细胞的新有效疗法的机会，这些静止细胞是肿瘤中的主要成分，在体内很有可能有效。

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