Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness
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abstract
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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.
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citation
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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.
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type
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journal paper/review (English)
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date of publishing
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03-01-2018
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journal title
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Oncoimmunology (7/4)
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ISSN print
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2162-4011
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pages
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e1414129
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PubMed
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29632733
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DOI
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10.1080/2162402X.2017.1414129
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