RESUMO
Colorectal cancer is the source of one of the most common cancer-related deaths worldwide, where the main cause of patient mortality remains metastasis. The aim of this study was to determine the role of CCL7 (chemokine (C-C motif) ligand 7) in tumor progression and finding whether it could predict survival of colorectal cancer patients. Initially, our study focused on the crosstalk between mesenchymal stem cells (MSCs) and CT26 colon carcinoma cells and resulted in identifying CCL7 as a chemokine upregulated in CT26 colon cancer cells cocultured with MSCs, compared with CT26 in monoculture in vitro. Moreover, we showed that MSCs enhance CT26 tumor cell proliferation and migration. We analyzed the effect of CCL7 overexpression on tumor progression in a murine CT26 model, where cells overexpressing CCL7 accelerated the early phase of tumor growth and caused higher lung metastasis rates compared with control mice. Microarray analysis revealed that tumors overexpressing CCL7 had lower expression of immunoglobulins produced by B lymphocytes. Additionally, using Jh mutant mice, we confirmed that in the CT26 model, CCL7 has an immunoglobulin-, and thereby, B-cell-dependent effect on metastasis formation. Finally, higher expression of CCL7 receptor CCR2 (C-C chemokine receptor type 2) was associated with shorter overall survival of colorectal cancer patients. Altogether, we showed that CCL7 is essentially involved in the progression of colorectal cancer in a CT26 mouse model and that the expression of its receptor CCR2 could be related to a different outcome pattern of patients with colorectal carcinoma.
Assuntos
Quimiocina CCL7/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Receptores CCR2/genética , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CCL7/análise , Neoplasias do Colo/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Receptores CCR2/análiseRESUMO
UNLABELLED: The AIM of work was to evaluate the alteration of the total proteolytic activity (TPA) and the levels of alpha(1)-proteinase inhibitor (alpha1PI) and alpha(2)-macroglobuline (alpha2M) in blood plasma of rats bearing Guerin carcinoma upon the development of Doxorubicin (DOX) resistance. MATERIALS AND METHODS: TPA and alpha1PI and alpha2M content in the blood plasma of male Wistar rats bearing DOX-resistant and DOX-sensitive Guerin carcinoma were evaluated by standard biochemical methods. RESULTS: During growth of both DOX-sensitive and DOX-resistant Guerin carcinoma, TPA decrease in blood plasma and the increase of alpha1PI levels were registered; in DOX-resistant group this effect was more pronounced. Alpha2M content in blood plasma of animals from both experimental groups was considerably smaller than that of the control and was the lowest in DOX-resistant group. CONCLUSION: The growth of DOX-resistant Guerin carcinoma is accompanied by imbalance of proteolysis processes in the blood plasma, particularly, alteration of TPA and alpha1PI and alpha2M levels.