RESUMO
Angiogenesis is crucial for tumor biology. There are many mechanisms by which tumors induce angiogenesis. We hypothesize that each individual tumor develops a unique mechanism to induce angiogenesis, and that activation of a particular angiogenic pathway suppresses the evolution of alternative pathways. We characterized 168 human non-small cell lung cancer (NSCLC) specimens for levels of angiogenic factors (angiogenic CXC chemokines, basic fibroblast growth factor, and vascular endothelial growth factor). We also induced lung tumor formation in A/J mice by injecting the tobacco carcinogen NNK. We dissected individual lung tumors and measured expression of angiogenic factors from three distinct families using real-time PCR. Finally, we controlled the angiogenic milieu using in vivo models to determine the resultant phenotype of the angiogenic factors expressed by NSCLC cells. Human tumors displayed marked variation in the expression of angiogenic factors. Individual mouse tumors, even from within the same mouse, displayed variability in their pattern of expression of angiogenic factors. In a sponge model of angiogenesis using murine lung cancer cells, implanting LLC cells with an angiogenic factor suppressed the expression of other angiogenic factors in implanted sponges. This suppressive effect was not seen in vitro. We conclude that lung cancer tumors evolve a unique and dominant angiogenic phenotype. Once an angiogenic pathway is activated, it may allow for tumor growth to proceed in the absence of a selection pressure to activate a second pathway.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/patologia , Variação Genética , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Neovascularização Patológica , Proteínas Angiogênicas/genética , Proteínas Angiogênicas/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Demografia , Feminino , Regulação Neoplásica da Expressão Gênica , Genes ras , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
A patient with risk factors of systemic lupus erythematosus, corticosteroid use, and malignancy received a diagnosis of concomitant pneumonia and osteomyelitis caused by Legionella longbeachae. In this report, the first description of Legionella osteomyelitis, previous cases of extrapulmonary Legionella infection are detailed.