RESUMO
Invasion of brain tumor cells has made primary malignant brain neoplasms among the most recalcitrant to therapeutic strategies. We tested whether the secreted protein Slit2, which guides the projection of axons and developing neurons, could modulate brain tumor cell invasion. Slit2 inhibited the invasion of medulloblastoma cells in a variety of in vitro models. The effect of Slit2 was inhibited by the Robo ectodomain. Time-lapse videomicroscopy indicated that Slit2 reduced medulloblastoma invasion rate without affecting cell direction or proliferation. Both medulloblastoma and glioma tumors express Robo1 and Slit2, but only medulloblastoma invasion is inhibited by recombinant Slit2 protein. Downregulation of activated Cdc42 may contribute to this differential response. Our findings reinforce the concept that neurodevelopmental cues such as Slit2 may provide insights into brain tumor invasion.
Assuntos
Meduloblastoma/patologia , Invasividade Neoplásica/prevenção & controle , Proteínas do Tecido Nervoso/fisiologia , Animais , Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Divisão Celular/efeitos dos fármacos , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Técnicas de Cocultura , Meios de Cultivo Condicionados , Glioma/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Cinética , Meduloblastoma/genética , Camundongos , Microscopia de Vídeo , Proteínas do Tecido Nervoso/genética , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Receptores Imunológicos/genética , Receptores Imunológicos/fisiologia , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Proteínas RoundaboutRESUMO
Pituitary adenomas are relatively common intracranial neoplasms that are frequently treated with surgical resection. Rapid visualization of pituitary tissue remains a challenge as current techniques either produce little to no information on hormone-secreting function or are too slow to practically aid in intraoperative or even perioperative decision-making. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) represents a powerful method by which molecular maps of tissue samples can be created, yielding a two-dimensional representation of the expression patterns of small molecules and proteins from biologic samples. In this chapter, we review the use of MALDI MSI, its application to the characterization of the pituitary gland, and its potential applications for guiding the management of pituitary adenomas.