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Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness

Maximilian Bösch, Lucas Onder, Hung-Wei Cheng, Mario Novkovic, Urs Mörbe, Sieghart Sopper, Guenther Gastl, Wolfram Jochum, Thomas Ruhstaller, Michael Knauer & Burkhard Ludewig

abstract The tumor microenvironment harbors cancer-associated fibroblasts that function as major modulators of cancer progression. Here, we assessed to which extent distinct cancer-associated fibroblast subsets impact mammary carcinoma growth and cancer cell stemness in an orthotopic murine model. We found that fibroblasts expressing the Cre recombinase under the control of the interleukin 7 promoter occupied mainly the tumor margin where they physically interacted with tumor cells. Intratumoral ablation of interleukin 7-expressing fibroblasts impaired breast tumor growth and reduced the clonogenic potential of cancer cells. Moreover, cDNA expression profiling revealed a distinct oncogenic signature of interleukin 7-producing fibroblasts. In particular, expression was strongly enhanced in interleukin 7-producing fibroblasts and cell type-specific genetic ablation and systemic pharmacological inhibition revealed that the CXCL12/CXCR4 axis impacts breast tumor cell stemness. Elevated expression of and other stem cell factors in primary human breast cancer-associated fibroblasts indicates that certain fibroblast populations support tumor cell stemness and thereby promote breast cancer growth.
   
citation Bösch M, Onder L, Cheng H W, Novkovic M, Mörbe U, Sopper S, Gastl G, Jochum W, Ruhstaller T, knauer m, Ludewig B. Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness. Oncoimmunology 2018; 7:e1414129.
   
type journal paper/review (English)
date of publishing 03-01-2018
journal title Oncoimmunology (7/4)
ISSN print 2162-4011
pages e1414129
PubMed 29632733
DOI 10.1080/2162402X.2017.1414129