The antimetastatic effect of a single low dose of cyclophosphamide involves modulation of galectin-1 and Bcl-2 expression.
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.
Rabinovich
Gabriel A
GA
Laboratorio de Inmunogenética, Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Rubinstein
Natalia
N
Matar
Pablo
P
Rozados
Viviana
V
Gervasoni
Silvia
S
Scharovsky
Graciela O
GO
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
D000276:Adjuvants, Immunologic; D018906:Antineoplastic Agents, Alkylating; D037483:Galectin 1; D006388:Hemagglutinins; D019253:Proto-Oncogene Proteins c-bcl-2; D003520:Cyclophosphamide