Local and systemic protumorigenic effects of cancer-associatedfibroblast- derived GDF15

Francesca Bruzzese, Christina Hägglöf, Alessandra Leone, Elin Sjöberg, Maria Serena Roca, Sara Kiflemariam, Tobias Sjöblom, Peter Hammarsten, Lars Egevad, Anders Bergh, Arne Östman, Alfredo Budillon, Martin Augsten

Research output: Contribution to journalArticlepeer-review

Abstract

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 TGFb/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. Cancer Res; 74(13); 3408-17.

Original languageEnglish
Pages (from-to)3408-3417
Number of pages10
JournalCancer Research
Volume74
Issue number13
DOIs
Publication statusPublished - Jul 1 2014

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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