Local and Systemic Protumorigenic Effects of Cancer-Associated Fibroblast-Derived GDF15
2014 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 13, 3408-3417 p.Article in journal (Refereed) Published
The tumor stroma is vital to tumor development, progression, and metastasis. Cancer-associated fibroblasts (CAF) are among the abundant cell types in the tumor stroma, but the range of their contributions to cancer pathogenicity has yet to be fully understood. Here, we report a critical role for upregulation of the TGF beta/BMP family member GDF15 (MIC-1) in tumor stroma. GDF15 was found upregulated in situ and in primary cultures of CAF from prostate cancer. Ectopic expression of GDF15 in fibroblasts produced prominent paracrine effects on prostate cancer cell migration, invasion, and tumor growth. Notably, GDF15-expressing fibroblasts exerted systemic in vivo effects on the outgrowth of distant and otherwise indolent prostate cancer cells. Our findings identify tumor stromal cells as a novel source of GDF15 in human prostate cancer and illustrate a systemic mechanism of cancer progression driven by the tumor microenvironment. Further, they provide a functional basis to understand GDF15 as a biomarker of poor prognosis and a candidate therapeutic target in prostate cancer.
Place, publisher, year, edition, pages
2014. Vol. 74, no 13, 3408-3417 p.
Cancer and Oncology Medical Genetics
IdentifiersURN: urn:nbn:se:uu:diva-229723DOI: 10.1158/0008-5472.CAN-13-2259ISI: 000338341700005OAI: oai:DiVA.org:uu-229723DiVA: diva2:738464