Growth pattern of de novo small clusters of colorectal cancer is regulated by Notch signaling at detachment

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancer Science Pub Date : 2024-09-19 DOI:10.1111/cas.16299
Yi-Kai Lin, Roberto Coppo, Kunishige Onuma, Hiroko Endo, Jumpei Kondo, Sadahiro Iwabuchi, Shinichi Hashimoto, Yoshiro Itatani, Kazutaka Obama, Masahiro Inoue
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引用次数: 0

Abstract

Cancer cell clusters have a higher capacity for metastasis than single cells, suggesting cancer cell clusters have biological properties different from those of single cells. The nature of de novo cancer cell clusters that are newly formed from tumor masses is largely unknown. Herein, we generated small cell clusters from colorectal cancer organoids and tracked the growth patterns of the clusters up to four cells. Growth patterns were classified into actively growing and poorly growing spheroids (PG). Notch signaling was robustly activated in small clusters immediately after dissociation, and Notch signaling inhibition markedly increased the proportion of PG spheroids. Only a limited number of PG spheroids grew under growth-permissive conditions in vitro, but xenograft tumors derived from Notch inhibited clusters showed growth rates comparable to those of untreated spheroids. Thus, de novo clusters are composed of cells with interchangeable growth fates, which are regulated in a context-dependent manner by Notch signaling.

Abstract Image

新发小簇结直肠癌的生长模式在脱落时受 Notch 信号调控。
与单细胞相比,癌细胞簇的转移能力更强,这表明癌细胞簇具有不同于单细胞的生物特性。从肿瘤块中新形成的癌细胞簇的性质在很大程度上是未知的。在此,我们从结直肠癌器官组织中生成了小细胞簇,并跟踪了最多四个细胞簇的生长模式。生长模式分为生长活跃球体(PG)和生长不良球体(PG)。Notch信号在小细胞簇解离后立即被激活,Notch信号抑制明显增加了PG球的比例。在体外允许生长的条件下,只有数量有限的PG球体生长,但从Notch抑制的集群中提取的异种移植肿瘤显示出与未经处理的球体相当的生长率。因此,新生细胞簇是由具有可互换生长命运的细胞组成的,这些细胞的生长命运受 Notch 信号的调控。
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来源期刊
Cancer Science
Cancer Science 医学-肿瘤学
自引率
3.50%
发文量
406
审稿时长
2 months
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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