DEVELOPMENT OF AN EXPERIMENTAL MODEL OF BONE METASTASIS FROM COLORECTAL CANCER

Introduction: Colorectal cancer has natural course well described in the literature and has effective therapy when instituted early. On the other hand, its still high mortality rate is due to the late demand for medical care in advanced stages of the disease, with 10% to 15% presenting metastases. The overall incidence of bone metastases in colorectal cancer patients is 5.5%. Indicator of poor prognosis, patients with bone metastases present mean survival less than 10 months and treatment is based on radiotherapy. There are few models of bone metastasis originating from colorectal cancer, and specifically for skullcap, because of the difficulty in offering radiotherapy, models of studies for new therapies are necessary. Objectives: The objective of this study is to develop an animal model of bone metastasis of colorectal adenocarcinoma with a view to the development of biomarkers and / or new therapeutic modalities. Methodology: After culture of human adenocarcinoma cells/ HT-29 xenotransplantation was performed in skullcap in athymic mice. After 30 days, anatomopathological (HE) study was performed to characterize bone metastasis in animals of both sexes. Results: There was growth of mass in the cranial region, with fixation in the skullcap and of infiltrative character in the bone. It was observed an inflammatory process with hyperemic areas, areas of necrosis and intense vascularization process; white, homogeneous, slightly lobulated, with “fish flesh” appearance, typical of colorectal adenocarcinoma findings. Microscopically, clusters of neoplastic cells with hyperchromatic nuclei, prominent nucleoli, and abundant cytoplasm consistent with metastatic colorectal carcinoma were observed. There was difference in tumor development in the different sexes. In males the tumors grew more and with higher speed. Area literature demonstrates that estrogens exert an antitumor effect through estrogen receptor-mediated signaling (ERs). ERβ acts as a dominant regulator, inducing reduction in ERα-mediated gene expression with a consequent negative effect on cell proliferation. Therefore, estrogen-mediated signaling plays a protective role in colorectal cancer. Conclusions: It was possible to develop an animal model of bone metastasis of colorectal carcinoma with a view to the development of biomarkers and / or new therapeutic modalities. Financial support: FAPESP Approval of the research ethics committee: 002.09.2015