Wt. Huang et al., Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation, CANCER RES, 61(23), 2001, pp. 8586-8594
Tenascin-C is an adhesion-modulatory extracellular matrix molecule that is
highly expressed in tumors. To investigate the effect of tenascin-C on tumo
r cells, we analyzed its antiadhesive nature and effect on tumor cell proli
feration in a fibronectin context. Glioblastoma and breast carcinoma cell a
dhesion was compromised by a mixed fibronectin/tenascin-C substratum, which
concomitantly caused increased tumor-cell proliferation. We identified the
antiadhesive mechanism as a specific interference of tenascin-C with cell
binding to the HepII/syndecan-4 site in fibronectin through direct binding
of tenascin-C to the 13th fibronectin type III repeat (FNIII13). Cell adhes
ion and proliferation levels were restored by the addition of FNIII13. Over
expression of syndecan-4, but not syndecan-1 or -2, reverted the cell adhes
ion defect of tenascin-C. We characterized FNIII13 as the binding site for
syndecan-4. Thus we describe a novel mechanism by which tenascin-C impairs
the adhesive function of fibronectin through binding to FNIII13, thereby in
hibiting the coreceptor function of syndecan-4 in fibronectin-induced integ
rin signaling.