Other Attachment Factors

In addition to collagen, fibronectin, laminin, and vitronectin, other components of the ECM and basement membrane also contribute to cell attachment. Thrombospondin is a large trimeric glycoprotein consisting of three identical 140-kDa subunits joined together through interchain disulfide linkages (155). Thrombospodin is released by activated platelets and is found associated with the ECM proteins heparin, collagen, laminin, and fibrinogen. Thrombospondin is synthesized by human long-term bone marrow cells in vitro, promotes the adhesion of hemato-poietic progenitor cells (156), and promotes the attachment and migration of monocytes and neutrophils (157). Receptors for thrombospondin that play a role in its function as an attachment factor include membrane-bound heparan sulphate (158), platelet glycoprotein IV (CD36;GPIIIb) (159), and av/^3 integrin (160).

Tenascin is a very large, star-shaped ECM glycopro-tein composed of six related subunits joined through interchain disulfide linkages. The individual subunits contain 13 epidermal growth factor-like repeats, 8 or more fibro-nectin type III repeats, and a globular carboxy-terminal fibronectin-like domain. Tenascin is associated with mesenchymal-epithelial interactions during development, tissue remodeling, and wound healing. Tenascin promotes the attachment of many cell types in vitro, including tumor cells, fibroblasts, and endothelial cells, in an RGD-dependent manner (161) through interaction with multiple integrins (162). Janusin, an ECM protein with structural homology to tenascin, promotes attachment and neurite outgrowth of hippocampal neurons in vitro (163).

Glycosaminoglycans are a major component of the ECM and, as already mentioned, bind to fibronectin (164), collagen (165), laminin (166), and vitronectin (127). Glycos-aminoglycans consist of long polysaccharide chains made up of disaccharide subunits and, with the exception of hy-aluronan (HA), are sulfated and covalently attach to core proteins through serine residues. In addition to playing a role in tissue formation during development and remodeling, glycosaminoglycans also contribute to the process of inflammation and tumorigenesis (167). One glycosamino-glycan that has been widely studied is HA. The role of HA in various cellular functions including cell proliferation, cell activation, and cell migration is dependent on its interaction with specific cell surface glycoprotein CD44 (168170). Molecular cloning of the CD44 gene revealed the presence of multiple isoforms, which result from alternate splicing. Analysis of the expression pattern of the different isoforms suggests that regulation of expression of specific isoforms plays a critical role in cellular interactions during early development (171). The CD44-HA interaction is involved in endothelial cell adhesion and proliferation (172) and T-cell adhesion and activation (173). CD44 has also been implicated in the regulation oftumor growth and metastasis, and this activity is dependent on its interaction with HA (174).

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