CD44/chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes
CD44/chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes
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DOI：
10.1091/mbc.7.3.383
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发表时间：
1996-03-01
影响因子：
3.3
通讯作者：
McCarthy, JB
中科院分区：
文献类型：
--
作者：
Knutson, JR;Iida, J;McCarthy, JB
肿瘤细胞对基底膜的侵袭是肿瘤转移过程中的关键步骤之一。肿瘤细胞对单个BM基质成分的识别可能涉及单个细胞黏附受体，如整合素或细胞表面蛋白多糖，也可能涉及两种受体的协同作用。在这项研究中，我们着重于鉴定细胞表面的CD44/硫酸软骨素蛋白多糖(CSPG)和人黑色素瘤细胞上的α2β1整合素，它们都通过IV型胶原依赖机制直接参与重组BM的体外侵袭。用Rho-硝基苯基-β-D-二甲基吡喃糖苷或抗CD44单抗预育干扰人黑色素瘤细胞表面CSPG的表达可通过重组BM抑制黑色素瘤细胞的侵袭。这些治疗方法也强烈地抑制黑色素瘤细胞在IV型胶原上的迁移，但它们并不能有效地抑制细胞与IV型胶原的黏附。纯化的黑色素瘤细胞表面CD44/CSPG或纯化的硫酸软骨素与IV型胶原亲和柱结合，与CD44/CSPG型TV胶原相互作用在介导肿瘤细胞侵袭中的作用一致。相反，黑色素瘤细胞在层粘连蛋白(LM)上的迁移不涉及CD44/CSPG，CD44/CSPG也不与LM结合，这表明CD44/CSPG-IV型胶原的相互作用在本质上是特异的。此外，抗α2和抗β1整合素单抗能够阻断黑色素瘤细胞对重组骨髓的侵袭。这两种抗整合素单抗均可抑制黑色素瘤细胞在TV型胶原上的黏附和迁移，而只有抗β1单抗可抑制黑色素瘤细胞与LM的黏附。综上所述，这些结果表明黑色素瘤细胞与IV型胶原的黏附是重组BM体外侵袭的重要考虑因素，提示CD44/CSPG和α2β1整合素可能在体内协同促进人黑色素瘤细胞的黏附、迁移和侵袭。
Tumor cell invasion of basement membranes (BM) represents one of the critical steps in the metastatic process. Tumor cell recognition of individual BM matrix components may involve individual cell adhesion receptors, such as integrins or cell surface proteoglycans, or may involve a coordinate action of both types of receptors. In this study, we have focused on the identification of a cell surface CD44/chondroitin sulfate proteoglycan (CSPG) and alpha 2 beta 1 integrin on human melanoma cells that are both directly involved in the in vitro invasion of reconstituted BM via a type IV collagen-dependent mechanism. Interfering with cell surface expression of human melanoma CSPG with either rho-nitrophenyl-beta-D-xylopyranoside treatment or anti-CD44 monoclonal antibody (mAb) preincubation inhibits melanoma cell invasion through reconstituted BM. These treatments also strongly inhibit melanoma cell migration on type IV collagen, however, they are ineffective at inhibiting cell adhesion to type IV collagen. Purified melanoma cell surface CD44/CSPG, or purified chondroitin sulfate, bind to type IV collagen affinity columns, consistent with a role for CD44/CSPG-type TV collagen interactions in mediating tumor cell invasion. In contrast, melanoma cell migration on laminin (LM) does not involve CD44/CSPG, nor does CD44/CSPG bind to LM, suggesting that CD44/CSPG-type IV collagen interactions are specific in nature. Additionally, anti-alpha 2 and anti-beta 1 integrin mAbs are capable of blocking melanoma cell invasion of reconstituted BM. Both of these anti-integrin mAbs inhibit melanoma cell adhesion and migration on type TV collagen, whereas only anti-beta 1 mAb inhibits cell adhesion to LM. Collectively, these results indicate that melanoma cell adhesion to type IV collagen is an important consideration in invasion of reconstituted BM in vitro, and suggest that CD44/CSPG and alpha 2 beta 1 integrin may collaborate to promote human melanoma cell adhesion, migration, and invasion in vivo.