RESUMO
Cell migration through the extracellular matrix (ECM) is necessary for cancer cells to invade adjacent tissues and metastasize to an organ distant from primary tumors. Highly invasive carcinoma cells form ECM-degrading membrane protrusions called invadopodia. Tumor-associated macrophages have been shown to promote the migratory phenotypes of carcinoma cells, and macrophages are known to form podosomes, similar structures to invadopodia. However, the role of invadopodia and podosomes in vivo remains to be determined. In this paper, we propose a model for possible functions and interactions of invadopodia and podosomes in tumor invasion, based on observations that macrophage podosomes degrade ECM and that podosome formation is regulated by colony-stimulating factor-1 signaling.
Assuntos
Citoesqueleto de Actina/fisiologia , Extensões da Superfície Celular/fisiologia , Invasividade Neoplásica , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Animais , Adesão Celular , Matriz Extracelular/fisiologia , Humanos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/ultraestrutura , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Neoplasias/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Schemes of the four-helix bundle surfaces of interleukin-2, -4, -5, granulocyte/macrophage-, granulocyte-, macrophage-colony-stimulating factor, interferon-beta, -gamma and growth hormone were designed. All cytokines appeared to have the structurally similar "holes" on the surfaces. They were suggested to serve as a part of the main receptor-binding sites.
Assuntos
Citocinas/ultraestrutura , Fator Estimulador de Colônias de Granulócitos/ultraestrutura , Hormônio do Crescimento/química , Interferon beta/ultraestrutura , Interferon gama/ultraestrutura , Interleucina-2/química , Interleucina-5/química , Fator Estimulador de Colônias de Macrófagos/ultraestrutura , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
Macrophage colony-stimulating factor (M-CSF) triggers the development of cells of the monocyte-macrophage lineage and has a variety of stimulatory effects on mature cells of this class. The biologically active form of M-CSF is a disulfide-linked dimer that activates an intrinsic tyrosine kinase activity on the M-CSF receptor by inducing dimerization of the receptor molecules. The structure of a recombinant human M-CSF dimer, determined at 2.5 angstroms by x-ray crystallography, contains two bundles of four alpha helices laid end-to-end, with an interchain disulfide bond. Individual monomers of M-CSF show a close structural similarity to the cytokines granulocyte-macrophage colony-stimulating factor and human growth hormone. Both of these cytokines are monomeric in their active form, and their specific receptors lack intrinsic tyrosine kinase activity. The similarity of these structures suggests that the receptor binding determinants for all three cytokines may be similar.
