title: The antimetastatic effect of a single low dose of cyclophosphamide involves modulation of galectin-1 and Bcl-2 expression.
abstract: We have demonstrated that a single low dose of cyclophosphamide has an antimetastatic effect on lymphoma (L-TACB)-bearing rats by modulating the host immune response. Galectin-1, a member of the galectin family with specificity for beta-galactosides, has potent immunomodulatory properties by regulating cell-matrix interactions and T-cell apoptosis. Since galectin-1 is expressed by highly metastatic tumors, in the present study we investigated the participation of this beta-galactoside-binding protein in cyclophosphamide-induced immunomodulation. Inbred " e" rats were s.c. challenged with L-TACB. After 14 days, half of the animals received an i.p. injection of cyclophosphamide (10 mg/kg), and on day 21 tumors and spleens were excised. Cell extracts were prepared and galectin-1 expression was determined by Western blot analysis and correlated with Bcl-2 expression levels and the DNA fragmentation profile. Expression of galectin-1 was significantly decreased in tumors from cyclophosphamide-treated rats compared to non-treated rats. The same effect was observed regarding expression of Bcl-2 by tumors. In contrast, expression of Bcl-2 was significantly higher in spleens from treated animals than in non-treated rats. This effect correlated with a decreased intensity in the pattern of DNA fragmentation of spleen cells from cyclophosphamide-treated animals. Our results suggest that a single low dose of cyclophosphamide modulates the expression of galectin-1 and Bcl-2 by tumors, which could in turn influence the apoptotic threshold of spleen mononuclear cells. This mechanism could explain, at least in part, the antimetastatic effect evidenced in our tumor experimental model.
authors.affiliation: Laboratorio de Inmunogenética, Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.forename: Natalia
authors.initials: N
authors.lastname: Rubinstein
authors.forename: Pablo
authors.initials: P
authors.lastname: Matar
authors.forename: Viviana
authors.initials: V
authors.lastname: Rozados
authors.forename: Silvia
authors.initials: S
authors.lastname: Gervasoni
authors.forename: Graciela O
authors.initials: GO
authors.lastname: Scharovsky
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D037483:Galectin 1; D006388:Hemagglutinins / Q000096:biosynthesis / Q000276:immunology*; D008207:Lymphatic Metastasis; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000276:immunology*; D051381:Rats
chemical_list: D000276:Adjuvants, Immunologic; D018906:Antineoplastic Agents, Alkylating; D037483:Galectin 1; D006388:Hemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D003520:Cyclophosphamide