Epidermal transformation leads to increased perlecan synthesis with heparin-binding-growth-factor affinity.
Perlecan, a proteoglycan of basement membrane and extracellular matrices, has important roles in both normal biological and pathological processes. As a result of its ability to store and protect growth factors, perlecan may have crucial roles in tumour-cell growth and invasion. Since the biological functions of different types of glycosaminoglycan vary with cellular origin and structural modifications, we analysed the expression and biological functions of perlecan produced by a normal epidermal cell line (JB6) and its transformed counterpart (RT101). Expression of perlecan in tumorigenic cells was significantly increased in both mRNA and protein levels. JB6 perlecan was exclusively substituted with heparan sulphate, whereas that of RT101 contained some additional chondroitin sulphate. Detailed structural analysis of the heparan sulphate (HS) chains from perlecan of both cell types revealed that their overall sulphation and chain length were similar (approximately 60 kDa), but the HS chains of tumour-cell-derived perlecan were less sulphated. This resulted from reduced 2-O- and 6-O-sulphation, but not N-sulphation, and an increase in the proportion of unsulphated disaccharides. Despite this, the heparan sulphate of RT101- and JB6-derived perlecan bound fibroblast growth factor-1, -2, -4 and -7 and heparin-binding epidermal growth factor with similar affinity. Therefore abundant tumour-derived perlecan may support the angiogenic responses seen in vivo and be a key player in tumorigenesis.
Tapanadechopone
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Department of Cell Biology, Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, 201C Volker Hall, 1670 University Blvd., Birmingham, Alabama 35294-0019, USA.
Tumova
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S
Jiang
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Couchman
J R
JR
D000818:Animals; D001483:Base Sequence; D002236:Carbohydrate Conformation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D004817:Epidermis / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000032:analysis; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D019763:Heparin Lyase / Q000378:metabolism; D051379:Mice; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D016220:Fibroblast Growth Factor 1; C071927:perlecan; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase; C021349:heparitinsulfate lyase