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

OncoImmunology

Thomas Ruhstaller¹  Michael Knauer¹  Urs Mörbe²  Burkhard Ludewig²  Maximilian Boesch²  Hung-Wei Cheng²  Lucas Onder²  Mario Novkovic²  Wolfram Jochum³  Guenther Gastl⁴  Sieghart Sopper⁴ 

[1] Breast Center, Kantonsspital St. Gallen;Institute of Immunobiology, Kantonsspital St. Gallen;Institute of Pathology, Kantonsspital St. Gallen;Internal Medicine V, Medical University of Innsbruck;

关键词: breast cancer;    tumor microenvironment;    interleukin 7;    cancer-associated fibroblast;    cancer stem cells;    cxcl12;   

DOI  :  10.1080/2162402X.2017.1414129

来源: DOAJ

【 摘 要 】

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, Cxcl12 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 CXCL12 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.

【 授权许可】

Unknown