Publication

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

Journal Paper/Review - Jan 3, 2018

Units
PubMed
Doi

Citation
Bösch M, Knauer M, Ruhstaller T, Jochum W, Gastl G, Sopper S, Mörbe U, Novkovic M, Cheng H, Onder L, 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)
Journal
Oncoimmunology 2018; 7
Publication Date
Jan 3, 2018
Issn Print
2162-4011
Pages
e1414129
Brief description/objective

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.