A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment

Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Marta Prieto-Vila, Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cancer-associated fibroblasts (CAFs) are one of the most prominent cell types in the stromal compartment of the tumor microenvironment. CAFs support multiple aspects of cancer progression, including tumor initiation, invasion, and metastasis. The heterogeneous nature of the stromal microenvironment is attributed to the multiple sources from which the cells in this compartment originate. The present study provides the first evidence that cancer stem cells (CSCs) are one of the key sources of CAFs in the tumor niche. We generated CSC-like cells by treating mouse induced pluripotent stem cells with conditioned medium from breast cancer cell lines. The resulting cell population expressed both CSC and pluripotency markers, and the sphere-forming CSC-like cells formed subcutaneous tumors in nude mice. Intriguingly, these CSC-like cells always formed heterogeneous populations surrounded by myofibroblast-like cells. Based on this observation, we hypothesized that CSCs could be the source of the CAFs that support tumor maintenance and survival. To address this hypothesis, we induced the differentiation of spheres and purified the myofibroblast-like cells. The resulting cells exhibited a CAF-like phenotype, suggesting that they had differentiated into the subpopulations of cells that support CSC self-renewal. These findings provide novel insights into the dynamic interplay between various microenvironmental factors and CAFs in the CSC niche.

Original languageEnglish (US)
Article number6838
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Tumor Microenvironment
Neoplastic Stem Cells
Myofibroblasts
Neoplasms
Stem Cell Niche
Cancer-Associated Fibroblasts
Induced Pluripotent Stem Cells
Stromal Cells
Conditioned Culture Medium
Nude Mice
Population
Maintenance
Breast Neoplasms
Neoplasm Metastasis
Phenotype
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Nair, N., Calle, A. S., Zahra, M. H., Prieto-Vila, M., Oo, A. K. K., Hurley, L., ... Seno, M. (2017). A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment. Scientific Reports, 7(1), [6838]. https://doi.org/10.1038/s41598-017-07144-5

A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment. / Nair, Neha; Calle, Anna Sanchez; Zahra, Maram Hussein; Prieto-Vila, Marta; Oo, Aung Ko Ko; Hurley, Laura; Vaidyanath, Arun; Seno, Akimasa; Masuda, Junko; Iwasaki, Yoshiaki; Tanaka, Hiromi; Kasai, Tomonari; Seno, Masaharu.

In: Scientific Reports, Vol. 7, No. 1, 6838, 01.12.2017.

Research output: Contribution to journalArticle

Nair, N, Calle, AS, Zahra, MH, Prieto-Vila, M, Oo, AKK, Hurley, L, Vaidyanath, A, Seno, A, Masuda, J, Iwasaki, Y, Tanaka, H, Kasai, T & Seno, M 2017, 'A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment', Scientific Reports, vol. 7, no. 1, 6838. https://doi.org/10.1038/s41598-017-07144-5
Nair, Neha ; Calle, Anna Sanchez ; Zahra, Maram Hussein ; Prieto-Vila, Marta ; Oo, Aung Ko Ko ; Hurley, Laura ; Vaidyanath, Arun ; Seno, Akimasa ; Masuda, Junko ; Iwasaki, Yoshiaki ; Tanaka, Hiromi ; Kasai, Tomonari ; Seno, Masaharu. / A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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