HSPGs enhance spontaneous and APRIL-induced HRS cell survival and proliferation. (A) Expression of syndecan-1 and syndecan-4 by HD-MyZ, L-428, KM-H2, and L-1236 HRS cells. Open and solid profiles correspond to experimental antibody and control antibody with irrelevant binding activity, respectively. (B) Binding of APRIL to HD-MyZ HRS cells pretreated with vehicle, heparinitase, heparinase, or heparin. Thin line corresponds to fluorescence of control streptavidin. Thick line corresponds to APRIL-binding activity of untreated HRS cells. Dashed line corresponds to APRIL-binding activity of HRS cells pretreated for 2 hours with control vehicle, heparinitase, heparinase, or heparin. Background fluorescence generated by control streptavidin was equivalent in HRS cells after various treatments. (C) Proliferation of HD-MyZ HRS cells exposed or not to APRIL after pretreatment with control vehicle, heparinitase, or heparinase. Cpm were converted into percentage of control as follows: cpm with pretreatment/cpm without pretreatment ×100. Bars indicate SD of 4 experiments; *P < .05 versus cells incubated with control vehicle (leftmost bar of each cluster). (D) Proliferation of HD-MyZ HRS cells exposed or not to APRIL in the presence of 0, 1, or 5 μg/mL heparin. Bars indicate SD of 3 experiments; *P < .05 versus cells incubated in the absence of heparin (leftmost bar of each cluster).