MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-a or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.

Regulamentação, concentração e instituições bancárias em contexto de crise

Dissertação de mestrado em Economia Monetária, Bancária e Financeira

The family haloplasmataceae

Haloplasmataceae is a family within the order Haloplasmatales, which currently includes one single genus and species: Haloplasma contractile. This family has unusual phenotypic features the most noticeable being a unique morphology and cellular contractility cycle and a distinct phylogenetic position between the Firmicutes and the Tenericutes (Mollicutes). Members of the Haloplasmataceae have been isolated from the upper sediments of a deep-sea anoxic brine in the Red Sea, but cultivation-independent studies have found related sequences in a wide range of biotopes including other extreme environments, contaminated soils and marine sediments, as well as intestinal samples. The isolation and description of new representatives of this family might therefore result in significant changes to the current description.

The Family Salinisphaeraceae

The family Salinisphaeraceae (Class Gammaproteobacteria, Order Salinisphaerales) comprises a single genus, Salinisphaera, and six species: S. shabanensis, S. hydrothermalis, S. dokdonensis, S. orenii, S. halophila, and S. japonica. All members of the family Salinisphaeraceae were isolated from marine/oceanic and high-salinity environments. These bacteria have coccoid or short rod morphologies and are halophilic or halotolerant. All known members of the family Salinisphaeraceae are heterotrophic, mesophilic aerobes, although S. hydrothermalis was shown to be a facultative chemolithoautotroph. Isolation and characterization of new members of the Salinisphaeraceae, as well as in-depth studies of the currently known species, will allow for a better understanding of this family.