Tenascin-C splice variant adhesive/anti-adhesive effects on chondrosarcoma cell attachment to fibronectin.
Tenascin-C is an oligomeric glycoprotein of the extracellular matrix that has been found to have both adhesive and anti-adhesive properties for cells. Recent elucidation of the two major TNC splice variants (320 kDa and 220 kDa) has shed light on the possibility of varying functions of the molecule based on its splicing pattern. Tenascin-C is prominently expressed in embryogenesis and in pathologic conditions such as tumorogenesis and wound healing. Fibronectin is a prominent adhesive molecule of the extracellular matrix that is often co-localized with tenascin-C in these processes. We studied the chondrosarcoma cell line JJ012 with enzyme-linked immunoabsorbance assays, cell attachment assays and antibody-blocking assays to determine the adhesive/anti-adhesive properties of the two major tenascin-C splice variants with respect to fibronectin and their effect on chondrosarcoma cell attachment. We found that the small tenascin-C splice variant (220 kDa) binds to fibronectin, whereas the large tenascin-C splice variant (320 kDa) does not. In addition, the small tenascin-C splice variant was found to decrease adhesion for cells when bound to fibronectin, but contributed to adhesion when bound to plastic in fibronectin-coated wells. Antibody blocking experiments confirmed that both the small tenascin-C splice variant and fibronectin contribute to cell adhesion when bound to plastic. The large tenascin-C splice variant did not promote specific cell attachment. We hypothesize that the biologic activity of tenascin-C is dependent on the tissue-specific splicing pattern. The smaller tenascin-C isoform likely plays a structural and adhesive role, whereas the larger isoform, preferentially expressed in malignant tissue, likely plays a role in cell egress and metastasis.
Ghert
M A
MA
Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
Qi
W N
WN
Erickson
H P
HP
Block
J A
JA
Scully
S P
SP
D017398:Alternative Splicing; D001665:Binding Sites; D002448:Cell Adhesion / Q000276:immunology; D002813:Chondrosarcoma / Q000473:pathology*; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D019063:Tenascin / Q000235:genetics* / Q000502:physiology*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D019063:Tenascin