Saleem Mohammad, Adhami Vaqar Mustafa, Zhong Weixiong, Longley B Jack, Lin Chen-Yong, Dickson Robert B, Reagan-Shaw Shannon, Jarrard David F, Mukhtar Hasan
Department of Dermatology, Laboratory of Medicine, University of Wisconsin, 1300 University Avenue, Medical Sciences Center, B-25, Madison, Wisconsin 53706, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):217-27. doi: 10.1158/1055-9965.EPI-05-0737.
Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix, and in the progression of some epithelial cancers. Here, we establish the clinical significance of matriptase and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), during the progression of human prostate cancer (CaP).
The expression patterns of matriptase and HAI-1 were determined in primary cultures of normal human prostate epithelial (NHPE) cells, human CaP cells LNCaP, DU-145, CWR22Rnu1, and PC-3, and in tissue samples of 172 patients with normal prostate, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma of different tumor grades.
The protein and mRNA levels of matriptase were significantly higher in all carcinoma cells as compared with NHPE cells. Conversely, all CaP cells exhibited a reduced expression of HAI-1 as compared with NHPE cells. A progressive increase in the protein levels of matriptase was observed with increasing tumor grade in CaP specimens as compared with normal and BPH tissue specimens. Tissue samples of normal prostate exhibited a high constitutive protein level of HAI-1 compared with BPH and low-grade cancer with a progressive loss with increasing tumor grade.
The increased expression of matriptase and loss of HAI-1 may be an important event during the progression of CaP in humans. We suggest that the ratio of these two gene products may serve as a promising biomarker for CaP progression and a potential marker for establishing the efficacy of therapeutic and chemopreventive interventions.
Matriptase是一种II型跨膜丝氨酸蛋白酶，参与血管生成、细胞外基质降解以及某些上皮癌的进展过程。在此，我们确定了Matriptase及其抑制剂肝细胞生长因子激活抑制剂-1（HAI-1）在人类前列腺癌（CaP）进展过程中的临床意义。
在正常人前列腺上皮（NHPE）细胞、人CaP细胞LNCaP、DU-145、CWR22Rnu1和PC-3的原代培养物中，以及在172例患有正常前列腺、良性前列腺增生（BPH）、前列腺上皮内瘤变（PIN）和不同肿瘤分级腺癌的患者的组织样本中，测定Matriptase和HAI-1的表达模式。
与NHPE细胞相比，所有癌细胞中Matriptase的蛋白质和mRNA水平均显著更高。相反，与NHPE细胞相比，所有CaP细胞中HAI-1的表达均降低。与正常和BPH组织样本相比，在CaP标本中观察到随着肿瘤分级增加，Matriptase的蛋白质水平逐渐升高。与BPH和低级别癌症相比，正常前列腺组织样本中HAI-1的组成性蛋白质水平较高，且随着肿瘤分级增加逐渐丧失。
Matriptase表达增加和HAI-1缺失可能是人类CaP进展过程中的一个重要事件。我们认为这两种基因产物的比例可能作为CaP进展的一个有前景的生物标志物，以及用于确定治疗和化学预防干预效果的潜在标志物。
