Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but increases metastases in TRAMP prostate cancer prone mice
Data(s) |
27/08/2012
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Resumo |
Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa) and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1fms) to produce syngeneic TRAMPfmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1fms and syngeneic C57BL/6 mice. Whilst TRAMPfmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU) tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care. |
Formato |
application/pdf |
Identificador | |
Publicador |
Public Library of Science |
Relação |
http://eprints.qut.edu.au/55081/1/Macrophage_Inhibitory_Cytokine.pdf http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043833 DOI:10.1371/journal.pone.0043833 Husaini, Yasmin, Qiu, Min Ru, Lockwood, Glen P., Luo, Xu Wei, Shang, Ping, Kuffner, Tamara, Tsai, Vicky Wang-Wei, Jiang, Lele, Russell, Pamela J., Brown, David A., & Breit, Samuel N. (2012) Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but increases metastases in TRAMP prostate cancer prone mice. PLoS ONE, 7(8), e43833. http://purl.org/au-research/grants/NHMRC/ |
Direitos |
Copyright 2012 Husaini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Fonte |
School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #111201 Cancer Cell Biology |
Tipo |
Journal Article |