Effects of transforming growth factor-beta in the development of inflammatory pseudotumour-like lesions in a murine model.
Alterations in transforming growth factor (TGF)-beta signalling have been frequently implicated in human cancer, and an important mechanism underlying its pro-oncogenic nature is suppression of the host antitumour immune response. Considering the immunosuppressive effect of TGF-beta, we asked whether human tumour cells, known to secrete TGF-beta in culture, would survive and grow when implanted into the peritoneal cavity of immunocompetent mice. Therefore, we developed a xenogeneic model where mice were intraperitoneally (i.p.) injected with a TGF-beta-secreting human colorectal adenocarcinoma cell line, LISP-A10. Although animals did not develop macroscopic tumours, the recovery and isolation of human tumour cells was achieved when an inflammatory environment was locally induced by the administration of complete Freund's adjuvant (CFA). This procedure significantly increased TGF-beta concentrations in the peritoneal fluid and was accompanied by impaired activation of the host-specific immune response against LISP-A10 cells. Furthermore, inflammatory lesions resembling human inflammatory pseudotumours (IPTs) were observed on the surface of i.p. organs. These lesions could be induced by either injection of LISP-A10 cells, cells-conditioned medium or recombinant TGF-beta but only after administration of CFA. In addition, host cyclooxygenase-2 and kinin receptors played an important role in the induction of TGF-beta-mediated IPT-like lesions in our experimental model.
Guariniello
Luciana Doria
LD
Department of Microbiology, Immunology and Parasitology, Federal University of Sao Paulo, Sao Paulo, Brazil.
Correa
Mariangela
M
Jasiulionis
Miriam Galvonas
MG
Machado
Joel
J
Silva
José Antônio
JA
Pesquero
João Bosco
JB
Carneiro
Célia Regina Whitaker
CR
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant / Q000494:pharmacology; D006104:Granuloma, Plasma Cell / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009368:Neoplasm Transplantation; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D043783:Receptor, Bradykinin B1; D016212:Transforming Growth Factor beta; D005620:Freund's Adjuvant