Colorectal Cancer Stem Cell Subtypes Orchestrate Distinct Tumor Microenvironments.

Autor:	Hosohama L; Department of Microbiology & Molecular Genetics, School of Medicine, University of California, Irvine, California., Tifrea DF; Department of Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, California.; Chao Family Comprehensive Cancer Center, University of California, Irvine, California., Nee K; Department of Biological Chemistry, School of Medicine, University of California, Irvine, California., Park SY; Department of Microbiology & Molecular Genetics, School of Medicine, University of California, Irvine, California., Wu J; Department of Biological Chemistry, School of Medicine, University of California, Irvine, California.; Chao Family Comprehensive Cancer Center, University of California, Irvine, California., Habowski AN; Department of Microbiology & Molecular Genetics, School of Medicine, University of California, Irvine, California., Van C; Department of Biological Chemistry, School of Medicine, University of California, Irvine, California., Seldin MM; Department of Biological Chemistry, School of Medicine, University of California, Irvine, California.; Chao Family Comprehensive Cancer Center, University of California, Irvine, California.; Cancer Research Institute, University of California, Irvine, California., Edwards RA; Department of Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, California.; Chao Family Comprehensive Cancer Center, University of California, Irvine, California.; Cancer Research Institute, University of California, Irvine, California., Waterman ML; Department of Microbiology & Molecular Genetics, School of Medicine, University of California, Irvine, California.; Chao Family Comprehensive Cancer Center, University of California, Irvine, California.; Cancer Research Institute, University of California, Irvine, California.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 27. Date of Electronic Publication: 2024 Apr 27.
DOI:	10.1101/2024.04.25.591144
Abstrakt:	Several classification systems have been developed to define tumor subtypes in colorectal cancer (CRC). One system proposes that tumor heterogeneity derives in part from distinct cancer stem cell populations that co-exist as admixtures of varying proportions. However, the lack of single cell resolution has prohibited a definitive identification of these types of stem cells and therefore any understanding of how each influence tumor phenotypes. Here were report the isolation and characterization of two cancer stem cell subtypes from the SW480 CRC cell line. We find these cancer stem cells are oncogenic versions of the normal Crypt Base Columnar (CBC) and Regenerative Stem Cell (RSC) populations from intestinal crypts and that their gene signatures are consistent with the "Admixture" and other CRC classification systems. Using publicly available single cell RNA sequencing (scRNAseq) data from CRC patients, we determine that RSC and CBC cancer stem cells are commonly co-present in human CRC. To characterize influences on the tumor microenvironment, we develop subtype-specific xenograft models and we define their tumor microenvironments at high resolution via scRNAseq. RSCs create differentiated, inflammatory, slow growing tumors. CBCs create proliferative, undifferentiated, invasive tumors. With this enhanced resolution, we unify current CRC patient classification schema with TME phenotypes and organization. Competing Interests: Declaration of Interests The authors declare no competing interests.
Databáze:	MEDLINE
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