RESUMO
Integrins are receptors that mediate cell adhesion and the formation of signaling complex. Changes in the expression of integrins are required during the following steps in the generation of metastases: a) angiogenesis; b) detachment from the primary tumor; c) tumor cell-platelet interaction; d) adhesion to vascular endothelium and e) proliferation. There is a correlation between invasive capability and changes in the expression of some proteins that are clustered in focal adhesion sites, as FAK, CD82, CD9 or CD63. Both, integrin blocking (using antibodies or RGD containing peptides), as well as induced changes in the expression of integrin-associated molecules, are able to inhibit formation of metastases. Discovery and characterization of molecules that regulate the adhesive capability of tumor cells, will lead to development of antimetastasic therapies. In the search of tumor dissemination inhibitors, integrins and some integrin-associated molecules are important pharmacological targets.
Assuntos
Desintegrinas/fisiologia , Integrinas/fisiologia , Metástase Neoplásica/prevenção & controle , Animais , Adesão Celular , Humanos , Modelos Biológicos , Invasividade Neoplásica , Transdução de SinaisRESUMO
Increased fibroblast replication and interstitial collagen accumulation occur commonly in the interstitial lung disease that progress to fibrosis. The processes controlling lung fibrogenesis are not completely understood, however. This study was designed to analyse the influence of T lymphocytes from lung tissue obtained at open lung biopsy from four patients with idiopathic pulmonary fibrosis and four patients with extrinsic allergic alveolitis on fibroblast proliferation and collagen synthesis in vitro. Lung T cell supernatants from patients with both diseases induced a moderate but significant inhibition of human lung fibroblast cell line growth. In contrast, there was a clear difference in the effect of T cells from the two groups of patients in relation to collagen production. Lung T lymphocytes from all four patients with idiopathic pulmonary fibrosis produced a substantial increase in collagen synthesis (from 371% to 514% of control values), whereas T cells from three of the four patients with extrinsic allergic alveolitis induced a significant decrease in collagen production (to 35%, 36%, and 43% of control values); in the fourth case there was an increase in collagen synthesis but this was lower than that seen with T cells from any of the patients with idiopathic pulmonary fibrosis. Peripheral T cells from six patients and control subjects caused a small increase in fibroblast proliferation and no change in collagen synthesis. The findings suggest that at least two types of interaction occur between lung T cells and fibroblasts in these disorders. A variable degree of inhibition of cell proliferation is observed in response to lung T cell supernatants from patients with both idiopathic pulmonary fibrosis and extrinsic allergic alveolitis; a substantial increase in collagen synthesis is triggered by lymphokines from patients with idiopathic pulmonary fibrosis.