Cohen I R, Murdoch A D, Naso M F, Marchetti D, Berd D, Iozzo R V
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Cancer Res. 1994 Nov 15;54(22):5771-4.
Abnormal expression of proteoglycans has been implicated in cancer and metastasis primarily because these macromolecules are involved in the control of cell growth and matrix assembly. In this report, we have investigated the expression and immunolocalization of perlecan, a major heparan sulfate proteoglycan of basement membranes and pericellular matrices, in human metastatic melanomas. Twenty-six of the 27 tumor samples showed a significant increase (up to 15-fold) in the perlecan mRNA levels when compared with normal tissue. This change correlated with a vast deposition of perlecan protein core in the pericellular matrix of metastatic melanomas. Furthermore, we have established a relationship between perlecan expression in clonal melanoma cells (70W) stimulated with neurotrophins and their increased invasiveness. Interestingly, perlecan mRNA levels were up-regulated within 10 min of neurotrophin stimulation, indicating that perlecan is an early response gene. This upregulation also occurred prior to heparanase production, suggesting that perlecan expression and its regulation might play a pivotal role in the initial onset of invasion.
蛋白聚糖的异常表达主要与癌症和转移有关，因为这些大分子参与细胞生长和基质组装的调控。在本报告中，我们研究了基底膜和细胞周围基质中的主要硫酸乙酰肝素蛋白聚糖——基底膜聚糖在人转移性黑色素瘤中的表达和免疫定位。与正常组织相比，27个肿瘤样本中有26个显示基底膜聚糖mRNA水平显著升高（高达15倍）。这种变化与基底膜聚糖蛋白核心在转移性黑色素瘤细胞周围基质中的大量沉积相关。此外，我们还建立了神经营养因子刺激的克隆性黑色素瘤细胞（70W）中基底膜聚糖表达与其侵袭性增加之间的关系。有趣的是，神经营养因子刺激后10分钟内基底膜聚糖mRNA水平即上调，表明基底膜聚糖是一个早期反应基因。这种上调也发生在乙酰肝素酶产生之前，提示基底膜聚糖的表达及其调控可能在侵袭的初始阶段起关键作用。
