Association of elevated levels of hyaluronidase, a matrix-degrading enzyme, with prostate cancer progression.
Association of elevated levels of hyaluronidase, a matrix-degrading enzyme, with prostate cancer progression.
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发表时间：
1996-02
期刊：
影响因子：
11.2
通讯作者：
V. Lokeshwar;B. Lokeshwar;Henri T. Pham;N. Block
中科院分区：
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作者：
V. Lokeshwar;B. Lokeshwar;Henri T. Pham;N. Block
细胞外基质成分和基质降解酶是肿瘤转移和血管生成的关键调控因子。透明质酸（HA）是一种基质糖胺聚糖，已知可促进肿瘤细胞粘附和迁移，其小片段具有血管生成作用。我们比较了正常成人前列腺（NAP）、良性前列腺增生（BPH）和前列腺癌（CaP）组织以及上皮外植体培养的条件培养基中透明质酸酶（一种降解HA的酶）的水平，采用了敏感底物（HA）凝胶测定法和elisa样测定法。结果显示，与NAP和BPH组织相比，肿瘤组织中该酶显著升高（3-10倍）。此外，组织中透明质酸酶水平与肿瘤分级密切相关。例如，局部扩展的CaP病变（191 +/- 7.9毫单位/毫克蛋白质）和低级别肿瘤（9.4 +/- 1.4毫单位/毫克蛋白质）的浓度分别为。在原代上皮外植体培养物中，CaP培养物分泌的透明质酸酶比NAP和BPH培养物分泌的透明质酸酶至少高10倍。此外，在已建立的前列腺癌细胞系中，DU145（雄激素无反应的转移细胞系）分泌的透明质酸酶是LNCaP（雄激素反应且分化相对良好的细胞系）的4倍。我们还表明，前列腺透明质酸酶的表观M(r)接近55000，pH值最适值为4.6，与其他具有良好特征的透明质酸酶不同。
Components of extracellular matrix and the matrix-degrading enzymes are some of the key regulators of tumor metastasis and angiogenesis. Hyaluronic acid (HA), a matrix glycosaminoglycan, is known to promote tumor cell adhesion and migration, and its small fragments are angiogenic. We have compared levels of hyaluronidase, an enzyme that degrades HA, in normal adult prostate (NAP), benign prostate hyperplasia (BPH) and prostate cancer (CaP) tissues and in conditioned media from epithelial explant cultures, using a sensitive substrate(HA)-gel assay and an ELISA-like assay. The results show a significant elevation (3-10-fold) of this enzyme in tumor tissues compared to that in NAP and BPH tissues. Furthermore, the hyaluronidase levels in tissues correlates well with the tumor grade. For example, the concentrations in a locally extended CaP lesion (191 +/- 7.9 milliunits/mg protein), and low-grade tumors (9.4 +/- 1.4 milliunits/mg protein), respectively. Among the primary epithelial explant cultures, CaP cultures secrete at least 10-fold higher levels of hyaluronidase that those secreted by NAP and BPH cultures. Furthermore, among the established prostate cancer cell lines, DU145, an androgen-unresponsive metastatic line, secretes 4-fold more hyaluronidase than LNCaP, an androgen-responsive and relatively well-differentiated cell line. We also show that prostatic hyaluronidase has an apparent M(r) approximate to 55,000, a pH optimum of 4.6, and is distinct from other well-characterized hyaluronidases.