Murry Brian P, Blust Bryan E, Singh Amandip, Foster Timothy P, Marchetti Dario
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, Louisiana 70803, USA.
J Cell Biochem. 2006 Feb 1;97(2):217-25. doi: 10.1002/jcb.20714.
Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate (HS) chains of proteoglycans (HSPG), and its expression has been associated with increased cell growth, invasion, and angiogenesis of tumors as well as with embryogenesis and tissue development. Since metastatic cancer cells express HPSE-1, we have developed an orthotopic brain slice model to study HPSE-1 involvement in brain-metastatic melanoma. This model allows for the characterization of tumor cell invasion at both quantitative and qualitative levels. Brain-metastatic melanoma cells (B16B15b) showed augmenting levels of HPSE-1 protein expression in a time-dependent manner. Secondly, B16B15b cells pre-treated with HPSE-1 showed a significant increase in the number of cells that invaded into the brain tissue. Finally, HPSE-1 exposure-augmented invasion depth in brain sections by brain-metastatic melanoma cells. We concluded that applying this brain slice model can be beneficial to investigate HPSE-1- related in vivo modalities in brain-metastatic melanoma and brain invasion in general. These results also further emphasize the potential relevance of using this model to design therapies for controlling this type of cancer by blocking HPSE-1 functionality.
乙酰肝素酶（HPSE-1）是一种内切β-D-葡萄糖醛酸酶，可切割蛋白聚糖（HSPG）的硫酸乙酰肝素（HS）链，其表达与肿瘤细胞的生长、侵袭、血管生成增加以及胚胎发生和组织发育有关。由于转移性癌细胞表达HPSE-1，我们开发了一种原位脑片模型来研究HPSE-1在脑转移性黑色素瘤中的作用。该模型能够在定量和定性水平上对肿瘤细胞的侵袭进行表征。脑转移性黑色素瘤细胞（B16B15b）的HPSE-1蛋白表达水平呈时间依赖性增加。其次，用HPSE-1预处理的B16B15b细胞侵入脑组织的细胞数量显著增加。最后，HPSE-1暴露增加了脑转移性黑色素瘤细胞在脑切片中的侵袭深度。我们得出结论，应用这种脑片模型有助于研究脑转移性黑色素瘤中与HPSE-1相关的体内模式以及一般的脑侵袭。这些结果还进一步强调了使用该模型设计通过阻断HPSE-1功能来控制这类癌症的疗法的潜在相关性。
