Although neutrophils have been linked to the formation of the pre-metastatic niche, the mechanism of their migration to distant uninvolved tissues has remained elusive. We report that bone marrow neutrophils from mice with early-stage cancers exhibited much more spontaneous migration to tissues. These cells lacked immunosuppressive activity but had elevated rates of oxidative phosphorylation and glycolysis, and much more production of ATP. Their enhanced spontaneous migration was mediated by the binding of ATP to purinergic receptors. In ectopic tumor models and the late stages of cancers, bone marrow neutrophils demonstrated potent immunosuppressive activity. However, these cells had metabolic and migratory activity indistinguishable from that of control neutrophils. A similar pattern of migration was observed in neutrophils and polymorphonuclear myeloid-derived suppressor cells from patients with cancer. These results elucidate the dynamic changes that neutrophils undergo in cancer and demonstrate the mechanism of neutrophils’ contribution to early tumor dissemination.
Amyloid precursor protein (APP) and its family members amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are type 1 transmembrane glycoproteins that are highly conserved across species. The transcriptional regulation of APP and APLP2 is similar but not identical, and the cleavage of both proteins is regulated by phosphorylation. APP has been implicated in Alzheimer's disease causation, and in addition to its importance in neurology, APP is deregulated in cancer cells. APLP2 is likewise overexpressed in cancer cells, and APLP2 and APP are linked to increased tumor cell proliferation, migration, and invasion. In this present review, we discuss the unfolding account of these APP family members’ roles in cancer progression and metastasis.
Immature Aedes mosquitoes were found in domestic, peridomestic, and tree hole habitats within three socioeconomic strata of Jodhpur, a city within an arid area of Rajasthan, India, endemic for dengue. Peridomestic habitats served as a persistent source of Aedes vectors, especially those used for watering cows for religious reasons that were located within high socioeconomic areas. Domestic (indoor) containers within low socioeconomic strata showed a higher container index (27.0%) than periurban areas with cattle sheds (14.3%) or high socioeconomic areas (18.1%). Mosquitoes were collected in tree holes at zoos and gardens supporting several species of monkeys. Six of 67 Aedes albopictus Skuse reared from immatures collected in tree holes tested positive for dengue antigen acquired through vertical transmission, possibly indicating a persistence mechanism for dengue virus within an urban environment.
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