Three-dimensional culture models mimic colon cancer heterogeneity induced by different microenvironments
Autor: | Kiyotaka Nakano, Etsuko Fujii, Masaya Yamazaki, Masami Suzuki, Masaki Yamazaki, Keita Shibuya, Shigeto Kawai |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Cancer microenvironment
Lung Neoplasms Colorectal cancer Cell Culture Techniques Notch signaling pathway Lumen (anatomy) lcsh:Medicine Biology Article Mice Cancer stem cell Cell Line Tumor Tumor Microenvironment medicine Animals Humans lcsh:Science Cell Proliferation Matrigel Multidisciplinary Lung Cancer stem cells Liver Neoplasms lcsh:R Cancer Cell Differentiation medicine.disease Phenotype Gene Expression Regulation Neoplastic medicine.anatomical_structure Colonic Neoplasms Neoplastic Stem Cells Cancer research lcsh:Q Amyloid Precursor Protein Secretases Neoplasm Transplantation Signal Transduction |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-020-60145-9 |
Popis: | 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. |
Databáze: | OpenAIRE |
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