Caracterização do perfil inflamatório e angiogênico associados ao desenvolvimento de tumores murinos

Abstract

Inflammation and angiogenesis are common features of almost, if not all tumors, however we found no studies that comparatively evaluated these processes in different types of tumors in order to identify the dominant pattern in tumors of different origins. The objectives of this study were to identify the patterns of these processes in murine experimental tumors of different origins (melanoma, breast and colon) and characterize vascular changes in the skin tissue adjacent to these tumors. Furthermore, we evaluated the contribution of acute and chronic inflammation in the development of mammary tumor using synthetic implants (polyether-polyurethane) to host 4T1 cells, 24 hours or 10 days post-implantation. The tumor cell inoculation (106) of B16F10, 4T1 and CT26.WT at the flank of mice resulted in tumor masses that differ among them. Melanomas were two times larger than the tumors of the colon and ten times greater than the mammary tumor. Locally, the CT26.WT cells induced higher number of vessels in the skin tissue adjacent to the tumor, but systemic levels of vascular endothelial growth factor (VEGF) were twice as high compared to the levels of the two other tumors. Inflammation as assessed by the enzyme myeloperoxidase (MPO) and N-acetyl--D-glucosaminidase (NAG) and the levels of inflammatory cytokines, tumor necrosis factor (TNF-) and chemokine CCL2 were more intense in the mammary tumor. The vascular index, determined by the amount of hemoglobin (Hb) and number of vessels in the most vascularized areas of the tumor, was twice higher in melanoma. The flow cytometric analysis of the cell population in 24h implants was predominantly of neutrophils (8.45 +/- 42.53%) and monocytes (37.53% +/- 7.48). In 10 day old implants, macrophages were the predominant cell population (37.10% +/- 4.54), followed by lymphocytes (28.1 +/- 4.77%) and monocytes (22:33 3:05 +/-%). The mammary tumor was two times bigger when developed in chronic inflammation when compared to tumors developed in acute phase of inflammation and five times higher compared with tumor developed without the inflammatory implant support. Inflammatory and angiogenic parameters were also more exacerbated in tumor bearing implants. Our results showed that different types of tumors have inflammatory and angiogenic growth and differential in the intensity components of the evaluated processes (growth, angiogenesis and inflammation). Furthermore, it was shown that chronic inflammation was more effective for the development of mammary tumor than acute inflammation. This study may have contribuited to elucidate the involvement of inflammation and angiogenesis in tumor progression, raising the possibility of a therapeutic approach for cancer based on the intensity of these tumor markers.