Comparative Analysis of Patient-Matched PDOs Revealed a Reduction in OLFM4-Associated Clusters in Metastatic Lesions in Colorectal Cancer.

Autor:	Okamoto T; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., duVerle D; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Yaginuma K; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Natsume Y; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Yamanaka H; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Kusama D; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Fukuda M; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Yamamoto M; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Perraudeau F; Graduate Group in Biostatistics, University of California, Berkeley, Berkeley, CA, USA., Srivastava U; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Kashima Y; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Suzuki A; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Kuze Y; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Takahashi Y; Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Ueno M; Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Sakai Y; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Noda T; Director's Room, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan., Tsuda K; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Suzuki Y; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan., Nagayama S; Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Yao R; Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: ryao@jfcr.or.jp.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2021 Apr 13; Vol. 16 (4), pp. 954-967. Date of Electronic Publication: 2021 Mar 11.
DOI:	10.1016/j.stemcr.2021.02.012
Abstrakt:	Metastasis is the major cause of cancer-related death, but whether metastatic lesions exhibit the same cellular composition as primary tumors has yet to be elucidated. To investigate the cellular heterogeneity of metastatic colorectal cancer (CRC), we established 72 patient-derived organoids (PDOs) from 21 patients. Combined bulk transcriptomic and single-cell RNA-sequencing analysis revealed decreased gene expression of markers for differentiated cells in PDOs derived from metastatic lesions. Paradoxically, expression of potential intestinal stem cell markers was also decreased. We identified OLFM4 as the gene most strongly correlating with a stem-like cell cluster, and found OLFM4 + cells to be capable of initiating organoid culture growth and differentiation capacity in primary PDOs. These cells were required for the efficient growth of primary PDOs but dispensable for metastatic PDOs. These observations demonstrate that metastatic lesions have a cellular composition distinct from that of primary tumors; patient-matched PDOs are a useful resource for analyzing metastatic CRC. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu