Timp3 loss accelerates tumour invasion and increases prostate inflammation in a mouse model of prostate cancer.

摘要: BACKGROUND Altered expression and activity of proteases is implicated in inflammation cancer progression. An important negative regulator protease TIMP3 (tissue inhibitor metalloproteinase 3). lacking many cancers including advanced prostate cancer, this may facilitate invasion metastasis by allowing unrestrained activity. METHODS To investigate the role progression, we crossed TIMP3-deficient mice (Timp3−/−) to with prostate-specific deletion tumor suppressor Pten (Pten−/−), a well-established mouse model cancer. Tumor growth progression were compared between Pten−/−, Timp3−/− control (Pten−/−, Timp3+/+) at 16 weeks age histopathology markers proliferation, vascularity, invasion. Metalloproteinase within tumors was assessed gelatin zymography. Inflammatory infiltrates immunohistochemistry for macrophages lymphocytes whereas cytokines other inflammatory mediators quantitative real time PCR multiplex ELISA. RESULTS Increased growth, proliferation index, increased microvascular density, observed Timp3+/+ tumors. cell associated matrix metalloprotease (MMP)-9 activation MMP-2. There markedly infiltration into along monocyte chemoattractant protein-1, cyclooxygenase-2, TNF-α, interleukin-1β; all which are cancer. CONCLUSIONS This study provides insights altered promoting implicates as an factor Prostate. © 2015 Wiley Periodicals, Inc.