Suppression of experimental lung colonization of mouse colon adenocarcinoma 26 in vivo by an anti-idiotype monoclonal antibody recognizing a platelet surface molecule.
The interaction between platelets and tumor cells is important in the formation of pulmonary metastasis. We previously established the 8F11 monoclonal antibody (mAb) by immunizing rats with the NL-17 cell line, a highly metastatic variant of mouse colon adenocarcinoma 26. 8F11 could inhibit the platelet aggregation in vitro and suppress the pulmonary metastasis in vivo by NL-17 cells. 8F11 recognized the Mr 44,000 sialoglycoprotein (gp44) on NL-17 cells, and the affinity-purified gp44 alone could induce platelet aggregation. Therefore, 8F11 might inhibit gp44-induced platelet aggregation by masking the epitope of gp44 that interacted with unknown molecule(s) on the platelet surface. To identify the platelet antigen that interacted with gp44, we generated anti-idiotype mAbs by immunizing rats with 8F11. Two of the established mAbs, AIP1 and AIP4, recognized not only 8F11 but also the Mr 160,000 platelet surface protein. AIP4 mAb could also inhibit the NL-17 cell-induced platelet aggregation in a dose-dependent manner. Furthermore, pretreatment of mice with AIP4 mAb suppressed the pulmonary metastasis of NL-17 cells in vivo. These results suggest that the Mr 160,000 platelet antigen participates in the NL-17 cell-induced platelet aggregation and colonization of NL-17 cells in the lung by interacting with the gp44 of NL-17 cells.
Kato
Y
Y
Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Japan.
Fujita
N
N
Yano
H
H
Tsuruo
T
T
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins