Faassen A E, Mooradian D L, Tranquillo R T, Dickinson R B, Letourneau P C, Oegema T R, McCarthy J B
Department of Laboratory Medicine, University of Minnesota Hospital and Clinics, Minneapolis 55455.
J Cell Sci. 1993 Jun;105 ( Pt 2):501-11. doi: 10.1242/jcs.105.2.501.
Tumor cell metastasis involves a complex series of events, including the adhesion, migration and invasive behavior of tumor cells on components of the extracellular matrix. Multiple cell surface receptors mediate interactions with the surrounding extracellular matrix and thereby influence cell adhesion, motility and invasion. We have previously described a cell surface CD44-related chondroitin sulfate proteoglycan on highly metastatic melanoma cells. CD44-chondroitin sulfate proteoglycan was shown to be important in melanoma cell motility and invasive behavior on type I collagen matrices. In our current studies, the role of cell surface CD44-chondroitin sulfate proteoglycan in collagen-mediated mouse melanoma cell migration and invasive behavior is further evaluated using transforming growth factor-beta 1. We report that transforming growth factor-beta 1 stimulates the migratory and invasive behavior of mouse melanoma cells on type I collagen. Transforming growth factor-beta 1 stimulated cell surface CD44-chondroitin sulfate proteoglycan synthesis in mouse melanoma cells, specifically through an upregulation of chondroitin sulfate production, while the expression of CD44-chondroitin sulfate proteoglycan core protein was not affected. Furthermore, transforming growth factor-beta 1-mediated enhancement of cell polarity, migration and invasive behavior on type I collagen gels was markedly inhibited in the presence of beta-D-xyloside, an agent that blocks chondroitin sulfate addition to the core protein. Collectively, our findings indicate that mouse melanoma cell surface CD44-chondroitin sulfate proteoglycan is required for transforming growth factor-beta 1-enhanced cell motility and invasion, and that CD44-chondroitin sulfate proteoglycan may play a role in forming and/or maintaining a dominant leading lamella, which is required for efficient locomotion.
肿瘤细胞转移涉及一系列复杂的事件，包括肿瘤细胞在细胞外基质成分上的黏附、迁移和侵袭行为。多种细胞表面受体介导与周围细胞外基质的相互作用，从而影响细胞黏附、运动和侵袭。我们之前曾描述过一种在高转移性黑色素瘤细胞上的细胞表面CD44相关硫酸软骨素蛋白聚糖。已证明CD44-硫酸软骨素蛋白聚糖在黑色素瘤细胞在I型胶原基质上的运动和侵袭行为中起重要作用。在我们目前的研究中，使用转化生长因子-β1进一步评估细胞表面CD44-硫酸软骨素蛋白聚糖在胶原介导的小鼠黑色素瘤细胞迁移和侵袭行为中的作用。我们报告转化生长因子-β1刺激小鼠黑色素瘤细胞在I型胶原上的迁移和侵袭行为。转化生长因子-β1刺激小鼠黑色素瘤细胞表面CD44-硫酸软骨素蛋白聚糖的合成，特别是通过上调硫酸软骨素的产生，而CD44-硫酸软骨素蛋白聚糖核心蛋白的表达不受影响。此外，在β-D-木糖苷存在下，转化生长因子-β1介导的细胞极性增强、在I型胶原凝胶上的迁移和侵袭行为明显受到抑制，β-D-木糖苷是一种阻止硫酸软骨素添加到核心蛋白的试剂。总的来说，我们的研究结果表明，小鼠黑色素瘤细胞表面CD44-硫酸软骨素蛋白聚糖是转化生长因子-β1增强细胞运动和侵袭所必需的，并且CD44-硫酸软骨素蛋白聚糖可能在形成和/或维持高效运动所需的优势前缘中发挥作用。
