Three-dimensional culture models mimic colon cancer heterogeneity induced by different microenvironments

Colorectal cancer demonstrates intra-tumour heterogeneity formed by a hierarchical structure comprised of cancer stem cells (CSCs) and their differentiated progenies. The mechanism by which CSCs are maintained and differentiated needs to be further elucidated, and there is evidence that the tumour m...

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Bibliographic Details
Published in:Scientific reports 2020-02, Vol.10 (1), p.3156-3156, Article 3156
Main Authors: Kawai, Shigeto, Yamazaki, Masaki, Shibuya, Keita, Yamazaki, Masaya, Fujii, Etsuko, Nakano, Kiyotaka, Suzuki, Masami
Format: Article
Language:English
Subjects:
Amyloid Precursor Protein Secretases - antagonists & inhibitors
Animal models
Animals
Cell culture
Cell Culture Techniques
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Colon cancer
Colonic Neoplasms - pathology
Colorectal cancer
Colorectal carcinoma
Gene Expression Regulation, Neoplastic
Humans
Liver
Liver Neoplasms - secondary
Lung Neoplasms - secondary
Mice
Microenvironments
Neoplasm Transplantation
Neoplastic Stem Cells - cytology
Phenotype
Phenotypes
Secretase
Signal Transduction
Stem cell transplantation
Stem cells
Tumor Microenvironment
Tumors
Xenografts
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Summary:Colorectal cancer demonstrates intra-tumour heterogeneity formed by a hierarchical structure comprised of cancer stem cells (CSCs) and their differentiated progenies. The mechanism by which CSCs are maintained and differentiated needs to be further elucidated, and there is evidence that the tumour microenvironment governs cancer stemness. Using PLR123, a colon cancer cell line with CSC properties, we determined the culture conditions necessary to establish a pair of three-dimensional (3D) culture models grown in Matrigel, designated stemCO and diffCO. The conditions were determined by comparing the phenotypes in the models with PLR123 mouse xenografts colonising lung and liver. StemCO resembled LGR5-positive undifferentiated tumours in the lung, and diffCO had lumen structures composed of polarised cells that were similar to the ductal structures found in differentiated tumours in the liver. In a case using the models for biomedical research, treatment with JAG-1 peptide or a γ-secretase inhibitor modified the Notch signaling and induced changes indicating that the signal participates in lumen formation in the models. Our results demonstrate that culture conditions affect the stemness of 3D culture models generated from CSCs and show that comparing models with different phenotypes is useful for studying how the tumour environment regulates cancer.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-60145-9