Type IV collagen-mediated melanoma cell adhesion and migration: involvement of multiple, distinct domains of the collagen molecule.
Type IV collagen-mediated melanoma cell adhesion and migration: involvement of multiple, distinct domains of the collagen molecule.
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发表时间：
1989-09
期刊：
影响因子：
11.2
通讯作者：
M. Chelberg;E. Tsilibary;A. Hauser;J. McCarthy
中科院分区：
文献类型：
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作者：
M. Chelberg;E. Tsilibary;A. Hauser;J. McCarthy
肿瘤细胞转移涉及一系列复杂的相互依赖的事件，包括基底膜的反复侵袭。几个实验室的研究表明，肿瘤细胞粘附和迁移响应层粘连蛋白作为肿瘤细胞侵袭的主要贡献因素。目前的研究致力于IV型胶原在促进肿瘤细胞粘附、扩散和迁移中的直接作用。IV型胶原介导的细胞行为的观察结果与I型胶原的细胞行为进行了对比。高转移性K1735 M4黑色素瘤细胞系以浓度依赖性方式粘附、扩散和迁移IV型胶原。使用定义明确的IV型胶原蛋白水解片段的功能测定表明，黑色素瘤细胞与该蛋白质的多个结构域相互作用。高转移性黑色素瘤细胞粘附，扩散，并表现出能动行为，以响应0.2至200 nM浓度的纯化的胃蛋白酶产生的，富含三螺旋结构域的IV型胶原蛋白。与此相反，细胞粘附和扩散，但基本上是nonmotile响应纯化的主要noncollagenous结构域的蛋白质。此外，从头蛋白质合成所需的细胞粘附的主要noncollagenous域，而粘附的螺旋结构域是依赖于从头蛋白质合成。用Arg-Gly-Asp（RGD）相关肽研究黑色素瘤细胞在IV型胶原上的粘附和铺展。结果表明，含有丝氨酸的RGD相关肽（GRGDSP）对黑色素瘤细胞粘附在IV型胶原包被的基质上几乎没有影响，而这种肽以浓度依赖性方式抑制黑色素瘤细胞粘附到纤连蛋白包被的基质上。相反，当苏氨酸取代丝氨酸（GRGDTP），细胞粘附到IV型胶原蛋白显着（45%）抑制。含苏氨酸的肽几乎消除了细胞粘附在涂有I型胶原的基质上。这些数据表明，黑色素瘤细胞在IV型胶原蛋白上的粘附、扩散和迁移具有复杂的分子基础，其部分依赖于RGD相关序列。
Tumor cell metastasis involves a complex series of interdependent events, including repeated invasion of basement membranes. Studies from several laboratories have implicated tumor cell adhesion and migration in response to laminin as a major contributing factor in tumor cell invasion. The current studies address the direct role of type IV collagen in promoting tumor cell adhesion, spreading, and migration. The observations of type IV collagen-mediated cellular behavior are contrasted with cellular behavior on type I collagen. The highly metastatic K1735 M4 melanoma cell line adhered, spread, and migrated in response to type IV collagen in a concentration-dependent manner. Functional assays using well-defined proteolytic fragments of type IV collagen demonstrated that melanoma cells interact with multiple domains of this protein. Highly metastatic melanoma cells adhered, spread, and exhibited motile behavior in response to 0.2 to 200 nM concentrations of a purified pepsin-generated, triple helix-rich domain of type IV collagen. In contrast, cells adhered and spread but were essentially nonmotile in response to a purified major noncollagenous domain of the protein. In addition, de novo protein synthesis was required for cell adhesion to the major noncollagenous domain, whereas adhesion to the helical domain was less dependent upon de novo protein synthesis. Arg-Gly-Asp (RGD)-related peptides were used to study the adhesion and spreading of melanoma cells on type IV collagen. The results demonstrated that a serine containing RGD-related peptide (GRGDSP) has virtually no effect on melanoma cell adhesion on type IV collagen-coated substrata, whereas this peptide inhibited melanoma cell adhesion to fibronectin-coated substrata in a concentration-dependent manner. In contrast, when threonine was substituted for serine (GRGDTP), cell adhesion to type IV collagen was significantly (45%) inhibited. The threonine-containing peptide virtually eliminated cell adhesion on substrata coated with type I collagen. These data demonstrate that adhesion, spreading, and migration of melanoma cells on type IV collagen have a complex molecular basis which is partially dependent on RGD-related sequences.