A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion.
A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion.
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DOI：
10.1083/jcb.116.2.521
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发表时间：
1992-01
期刊：
影响因子：
--
通讯作者：
McCarthy JB
中科院分区：
文献类型：
--
作者：
Faassen AE;Schrager JA;Klein DJ;Oegema TR;Couchman JR;McCarthy JB
肿瘤细胞的转移扩散通过一系列复杂的事件发生，其中之一涉及肿瘤细胞与细胞外基质（ECM）组分的粘附。粘附的肿瘤细胞的细胞表面受体与周围ECM之间的多种相互作用有助于细胞运动和侵袭。目前的研究评估的作用，细胞表面硫酸软骨素蛋白聚糖（CSPG）的粘附，运动性和侵袭行为的高转移性小鼠黑色素瘤细胞系（K1735 M4）的I型胶原基质。通过用对硝基苯基β-D-吡喃木糖苷（β-D-木糖苷）（一种使硫酸软骨素与CSPG核心蛋白合成解偶联的化合物）阻断小鼠黑素瘤细胞产生CSPG，我们观察到黑素瘤细胞在I型胶原上的运动性和侵入I型胶原凝胶的行为相应降低。黑色素瘤细胞在I型胶原上的运动也可以通过用软骨素酶去除细胞表面硫酸软骨素来抑制。相比之下，I型胶原介导的黑色素瘤细胞粘附和扩散不受β-D-木糖苷或软骨素酶治疗的影响。这些结果表明，小鼠黑色素瘤CSPG不是一个主要的细胞粘附受体，但可能发挥作用，在黑色素瘤细胞的运动和侵袭水平的细胞易位。此外，纯化的小鼠黑色素瘤细胞表面CSPG显示，通过亲和色谱法和固相结合试验，结合I型胶原蛋白和这种相互作用被证明是介导的，至少部分地，由硫酸软骨素。此外，我们已经确定，小鼠黑色素瘤CSPG是由一个110 kD的核心蛋白，是由抗CD 44抗体识别的蛋白质印迹。总的来说，我们的数据表明，细胞表面CD 44相关的CSPG和I型胶原之间的相互作用，在ECM中可能发挥重要作用，在小鼠黑色素瘤细胞的运动和入侵，硫酸软骨素部分的蛋白多糖似乎是一个关键的组成部分，在介导这种效果。
The metastatic spread of tumor cells occurs through a complex series of events, one of which involves the adhesion of tumor cells to extracellular matrix (ECM) components. Multiple interactions between cell surface receptors of an adherent tumor cell and the surrounding ECM contribute to cell motility and invasion. The current studies evaluate the role of a cell surface chondroitin sulfate proteoglycan (CSPG) in the adhesion, motility, and invasive behavior of a highly metastatic mouse melanoma cell line (K1735 M4) on type I collagen matrices. By blocking mouse melanoma cell production of CSPG with p- nitrophenyl beta-D-xylopyranoside (beta-D-xyloside), a compound that uncouples chondroitin sulfate from CSPG core protein synthesis, we observed a corresponding decrease in melanoma cell motility on type I collagen and invasive behavior into type I collagen gels. Melanoma cell motility on type I collagen could also be inhibited by removing cell surface chondroitin sulfate with chondroitinase. In contrast, type I collagen-mediated melanoma cell adhesion and spreading were not affected by either beta-D-xyloside or chondroitinase treatments. These results suggest that mouse melanoma CSPG is not a primary cell adhesion receptor, but may play a role in melanoma cell motility and invasion at the level of cellular translocation. Furthermore, purified mouse melanoma cell surface CSPG was shown, by affinity chromatography and in solid phase binding assays, to bind to type I collagen and this interaction was shown to be mediated, at least in part, by chondroitin sulfate. Additionally we have determined that mouse melanoma CSPG is composed of a 110-kD core protein that is recognized by anti-CD44 antibodies on Western blots. Collectively, our data suggests that interactions between a cell surface CD44-related CSPG and type I collagen in the ECM may play an important role in mouse melanoma cell motility and invasion, and that the chondroitin sulfate portion of the proteoglycan seems to be a critical component in mediating this effect.