Abstract 435: Adipocyte-derived monocyte chemotactic protein-1 (MCP-1) promotes prostate cancer progression through matrix metalloproteinase (MMP-2) mediated extracellular matrix degradation
Abstract Background: Obesity is known to be associated with prostate cancer development and progression, but the detailed mechanism is not clear. Monocyte chemotactic protein-1 (MCP-1) is secreted from cancer cells, stromal cells and adipocytes, and it is involved in prostate cancer progression. Her...
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Published in | Cancer research (Chicago, Ill.) Vol. 75; no. 15_Supplement; p. 435 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.08.2015
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Online Access | Get full text |
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Summary: | Abstract
Background: Obesity is known to be associated with prostate cancer development and progression, but the detailed mechanism is not clear. Monocyte chemotactic protein-1 (MCP-1) is secreted from cancer cells, stromal cells and adipocytes, and it is involved in prostate cancer progression. Here we investigated the biological role of MCP-1 secreted from adipocytes for prostate cancer cells.
Methods: Human pre-adipocytes (HPAds) were cultured and differentiated to mature adipocytes. Conditioned medium (CM) from HPAd cells was obtained using phenol red-free RPMI1640 medium. We performed a cytokine membrane array analysis to detect cytokines in the CM. To characterize the physiological function of MCP-1 in the CM, we performed an MTT-assay, a wound-healing and invasion assay with anti-MCP-1 antibody using three prostate cancer cell lines: DU145, LNCaP, and PC-3. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were evaluated by gelatin zymography. A qPCR and Western blotting were used to examine the mRNA and protein expression levels of MMP-2.
Results: The cytokine membrane array of the CM showed a strong signal of MCP-1compared to the control medium, and we thus focused our attention on MCP-1 in the CM. The CM up-regulated the cancer cell proliferation, and the neutralization by anti-MCP-1 antibody inhibited the proliferative effect of the prostate cancer cell lines. The CM greatly increased the invasive activity in the prostate cancer cell lines, and anti-MCP-1 antibody decreased the invasiveness. Gelatin zymography revealed that the CM markedly enhanced the enzymatic activity of MMP-2, and anti-MCP-1 antibody down-regulated its effect. MMP-2 mRNA expression was undetected and the MMP-2 protein level was unchanged between the control medium and CM in DU145 cells.
Conclusions: MCP-1 from adipocytes enhances the growth and invasion activity of prostate cancer cells. The inhibition of MCP-1 derived from adipocytes might be an effective treatment for prostate cancer.
Citation Format: Yusuke Ito, Hitoshi Ishiguro, Naohito Kobayashi, Hisashi Hasumi, Masatoshi Watanabe, Masahiro Yao, Hiroji Uemura. Adipocyte-derived monocyte chemotactic protein-1 (MCP-1) promotes prostate cancer progression through matrix metalloproteinase (MMP-2) mediated extracellular matrix degradation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 435. doi:10.1158/1538-7445.AM2015-435 |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.AM2015-435 |