RESUMEN
The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.
Asunto(s)
Neoplasias de la Mama/patología , Transformación Celular Neoplásica/patología , Neoplasias Mamarias Experimentales/patología , Células Madre Neoplásicas/patología , Receptores CCR7/genética , Receptores CCR7/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/patología , Glándulas Mamarias Humanas/metabolismo , Glándulas Mamarias Humanas/patología , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Madre Neoplásicas/metabolismo , Receptores CCR7/deficienciaRESUMEN
Having witnessed a large increase in Mycobacterium tuberculosis notifications in south London, we wanted to ascertain the prevalence of HIV and tuberculosis co-infection in our patients. All patients with tuberculosis and their contacts were anonymously tested for HIV in blood and saliva, respectively. 11.4% of patients (from various demographic groups) with tuberculosis who attend chest clinics in south London are HIV positive. In addition, 5% of individuals seen in the tuberculosis contact screening clinics and 4% new entrants are HIV positive. All patients with Mycobacterium tuberculosis, irrespective of background, should be urged to have an HIV test.