INHIBITION OF TUMOR-CELL ADHESION TO LYMPH-NODES BY LAMININ-RELATED PEPTIDE AND NEURAMINIDASE

Background Adhesion to lymph nodes, rather than growth stimulation, ac counted for preferential colonization of lymph nodes by a metastatic B 16 melanoma. We investigated these adhesive interactions. Methods. Fou r classes of molecules were tested for inhibition of melanoma adhesion to cryostat sections of lymph node. Results. Calcium chelators ethyle nediaminetetraacetic acid and l-bis-(beta-aminoethylether)-N,N,N',N'-t etraacetic acid completely inhibited adhesion (50% adhesion, half-maxi mal inhibition, at 1 to 3 mmol/L). Cytochalasin B, which impairs contr actile microfilaments, inhibited adhesion (60% adhesion at .001 mmol/L , 28% at .01 mmol/L). Colchicine, which disaggregates microtubules, ha d a similar effect (20% at .01 mmol/L, lowest dose tested). Trypsin sl ightly increased adhesion (125% adhesion at 10 mug/ml). Neuraminidase, which removed sialic acid residues, inhibited it (50% adhesion at 5 m ug/ml). Gly-arg-gly-asp-ser, a peptide with a cell binding sequence of fibronectin, did not consistently inhibit adhesion (69% adhesion at 0 .1 mg/ml, 83% adhesion at 1 mg/ml) or substantially differ from gly-ar g-gly-glu-ser-pro (59% adhesion at 0.1 mg/ml, 90% adhesion at 1 mg/ml) . In contrast, a peptide with a cell binding region of laminin (tyr-il e-gly-ser-arg) inhibited adhesion (50% adhesion at .05 mg/ml). Conclus ions. Tumor cell-lymph node adhesion is a calcium-dependent process, r equiring a functional cytoskeleton, that is mediated by both sialic ac id moieties and trypsin-resistant, laminin-related, adhesion molecules .