Local and Systemic Protumorigenic Effects of Cancer-Associated Fibroblast-Derived GDF15

被引：123

作者：

Bruzzese, Francesca ^{[1
]}

Hagglof, Christina ^{[2
]}

Leone, Alessandra ^{[1
]}

Sjoberg, Elin ^{[4
]}

Roca, Maria Serena ^{[1
]}

Kiflemariam, Sara ^{[3
]}

Sjoblom, Tobias ^{[3
]}

Hammarsten, Peter ^{[2
]}

Egevad, Lars ^{[4
]}

Bergh, Anders ^{[2
]}

Ostman, Arne ^{[4
]}

Budillon, Alfredo ^{[1
]}

Augsten, Martin ^{[4
]}

机构：

[1] Fdn Giovanni Pascale IRCCS, Ist Nazl Studio & Cura Tumori, Naples, Italy

[2] Umea Univ, Dept Med Biosci, Umea, Sweden

[3] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[4] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

来源：

CANCER RESEARCH | 2014年 / 74卷 / 13期

基金：

瑞典研究理事会;

关键词：

MACROPHAGE-INHIBITORY CYTOKINE-1; PROSTATE-CANCER; GROWTH-FACTOR; TUMOR-GROWTH; COLORECTAL-CANCER; H6D POLYMORPHISM; AUTOCRINE FACTOR; STROMAL CELLS; EXPRESSION; BETA;

D O I：

10.1158/0008-5472.CAN-13-2259

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C)2014 AACR.

引用

页码：3408 / 3417

页数：10

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