A monoclonal antibody to Lewis lung carcinoma variant H-59 identifies a plasma membrane protein with apparent relevance to lymph node adhesion and metastasis.
Tumors H-59 and M-27, two stable metastatic variants of the Lewis lung carcinoma, differ in their ability to disseminate lymphatically. Tumor H-59 metastasizes to the regional lymph nodes regardless of the local site of growth and gives rise to widespread lymphatic dissemination, whereas tumor M-27 disseminates hematogenously without involvement of the regional nodes (P. Brodt, Cancer Res., 46: 2442-2448, 1986). In a previous paper we reported that this divergent potential to disseminate lymphatically correlated well with adhesion to frozen sections of syngeneic lymph nodes and spleens (P. Brodt, Clin. Exp. Metastasis, 7: 343-352, 1989). A monoclonal antibody (12/50) specific for tumor H-59 was subsequently generated. This antibody (an IgG1) but not three control antibodies, which reacted with tumor H-59, significantly reduced tumor cell binding to the frozen sections. Western blot analysis revealed that it recognized a plasma membrane protein of Mr 37,000 on tumor H-59 cells. No antibody binding was detected when solubilized plasma membrane preparations of tumor M-27 were used. Subsequent enzymatic assays indicated that the binding of monoclonal antibody 12/50 was insensitive to cell treatment with exoglycosidases but could be significantly reduced by pretreatment of the tumor cells with Pronase. Together these results suggest that monoclonal antibody 12/50 recognizes a cell surface adhesion protein relevant to lymphatic dissemination of this tumor.
Department of Surgery, McGill University, Montreal, Quebec, Canada.
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Shestowsky
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Fallavollita
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Brodt
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000302:isolation & purification; D002448:Cell Adhesion; D002460:Cell Line; D005260:Female; D005455:Fluorescent Antibody Technique; D014644:Genetic Variation; D006867:Hydrolases; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009362:Neoplasm Metastasis
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D008565:Membrane Proteins; D006867:Hydrolases