Publikation
Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness
Wissenschaftlicher Artikel/Review - 03.01.2018
Bösch Maximilian, Knauer Michael, Ruhstaller Thomas, Jochum Wolfram, Gastl Guenther, Sopper Sieghart, Mörbe Urs, Novkovic Mario, Cheng Hung-Wei, Onder Lucas, Ludewig Burkhard
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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.