A specific cell surface glycoconjugate controlling cell motility: evidence by functional monoclonal antibodies that inhibit cell motility and tumor cell metastasis.
The biochemical basis of cell motility has been viewed as a complex process involving cell surface membrane proteins, integrin receptors, growth factors and their receptors, and cytoskeletal components [Rosen & Goldberg (1989) In Vitro 25, 1079]. The possible involvement of glycoconjugates at the cell surface in controlling cell motility has not been systematically investigated. We addressed this question using functional monoclonal antibodies (MAbs), which inhibit cell motility and the metastatic potential of tumor cells, as probes. Two such MAbs, derived from two independent processes of immunization and selection, were found to directed to a common specific carbohydrate structure, Fuc alpha 1----2Gal beta 1----R. MAb MIA-15-5 was established after immunization of mice with small cell lung carcinoma line PC7 and selected on the basis of inhibition of U937 and HEL cell migration. MAb MIA-22-20 was established after immunization with lung adenocarcinoma line MAC-10 and selected on the basis of inhibition of MAC-10 cell migration. These two MAbs were both IgM and were consistently reactive with the Fuc alpha 1----2Gal beta 1----R structure, regardless of the identity of the R group. Various other anti-H MAbs, specific to carrier isotype, did not affect cell motility. MAb MIA-15-5 reacted with 30-40% of high-metastatic variant BL6 of mouse melanoma B16 line but with only less than 5% of low-metastatic variant F1. Metastatic deposition to lung after injection of BL6 cells was inhibited if MAb MIA-15-5 was injected within 3 h but was not inhibited by injection of other anti-H antibodies under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Miyake
M
M
Biomembrane Institute, Seattle, Washington 98119.
Hakomori
S I
SI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000954:Antigens, Surface / Q000276:immunology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D006001:Glycoconjugates / Q000502:physiology*; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000473:pathology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006001:Glycoconjugates