Effects of transforming growth factor-beta in the development of inflammatory pseudotumour-like lesions in a murine model

Abstract

Alterations in transforming growth factor (TGF)-beta signalling have been frequently implicated in human cancer, and an important mechanism underlying its pro-oncogenic pature is suppression of the host antitumour immune response. Considering the immunosuppressive effect of TGF-beta, we asked whether human turnout 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 tumouts, the recovery and isolation of human turnout 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 LlSP-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.