Lichtinghagen Ralf, Musholt Petra B, Stephan Carsten, Lein Michael, Kristiansen Glen, Hauptmann Steffen, Rudolph Birgit, Schnorr Dietmar, Loening Stefan A, Jung Klaus
Department of Clinical Chemistry, University Medical School, Hannover, Germany.
Anticancer Res. 2003 May-Jun;23(3B):2617-24.
Increased expression of matrix metalloproteinases (MMPs) was found in various carcinomas. The aim of this study was to present a comprehensive mRNA expression profile of MMPs in benign and malignant prostatic tissue.
mRNA expression patterns of MMP-1, -2, -7, -9, -11, -14 and their tissue inhibitors (TIMPs) -1, -2 and -3 were studied in cancerous and non-cancerous parts of 17 prostates removed by radical prostatectomy. Competitive reverse transcritpion PCR was used for quantification of MMP and TIMP mRNA.
Both decreased (MMP-2, MMP-11, MMP-14) and a tendency to increased (MMP-9) MMP values in cancerous compared to the non-cancerous samples were observed. Significantly reduced TIMP-2 and TIMP-3 values were remarkable. Relatively strong associations were found among the three TIMPs while only a significant correlation between MMPs was observed between MMP-2 and MMP-7. There were no significant correlations between MMPs and tumor grade and stage and serum prostate-specific antigen. Receiver operation characteristic analyses proved that MMP and TIMP mRNA and their ratios have an insufficient capability to differentiate between cancerous and non-cancerous tissue. The ratios of MMP-9 to all three TIMPs and the ratio of MMP-14 to TIMP-3 were significantly increased.
These increased ratios support the view of an imbalance between MMP-9 activity and its inhibitory counterparts in cancerous tissue as an important step in the development of prostate carcinoma and implicate the rationale of using synthetic inhibitors of MMPs as potential therapeutic tools.
在多种癌症中发现基质金属蛋白酶（MMPs）的表达增加。本研究的目的是呈现良性和恶性前列腺组织中MMPs的全面mRNA表达谱。
对17例接受根治性前列腺切除术切除的前列腺的癌组织和非癌组织中MMP-1、-2、-7、-9、-11、-14及其组织抑制剂（TIMPs）-1、-2和-3的mRNA表达模式进行了研究。采用竞争性逆转录PCR对MMP和TIMP mRNA进行定量。
与非癌样本相比，癌组织中观察到MMP值降低（MMP-2、MMP-11、MMP-14）以及MMP-9有升高趋势。TIMP-2和TIMP-3值显著降低。在三种TIMP之间发现了相对较强的关联，而在MMP之间仅观察到MMP-2和MMP-7之间有显著相关性。MMP与肿瘤分级、分期及血清前列腺特异性抗原之间无显著相关性。受试者操作特征分析证明，MMP和TIMP mRNA及其比值区分癌组织和非癌组织的能力不足。MMP-9与所有三种TIMP的比值以及MMP-14与TIMP-3的比值显著升高。
这些升高的比值支持了癌组织中MMP-9活性与其抑制物之间失衡是前列腺癌发生发展的重要步骤这一观点，并暗示了使用MMPs合成抑制剂作为潜在治疗工具的合理性。
