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Effects of transforming growth factor‐β in the development of inflammatory pseudotumour‐like lesions in a murine model
Author(s) -
Guariniello Luciana Doria,
Correa Mariangela,
Jasiulionis Miriam Galvonas,
Machado Joel,
Silva José Antônio,
Pesquero João Bosco,
Carneiro Célia Regina Whitaker
Publication year - 2006
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2006.00471.x
Subject(s) - transforming growth factor , immune system , transforming growth factor beta , cancer research , immunology , peritoneal cavity , inflammation , biology , chemokine , medicine , microbiology and biotechnology , anatomy
Summary Alterations in transforming growth factor (TGF)‐β 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‐β, we asked whether human tumour cells, known to secrete TGF‐β 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‐β‐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‐β 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‐β but only after administration of CFA. In addition, host cyclooxygenase‐2 and kinin receptors played an important role in the induction of TGF‐β‐mediated IPT‐like lesions in our experimental model.