Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis

Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed

Paid Crowdsourcing, Low Income Contributors, and Subjectivity

Scientific projects that require human computation often resort to crowdsourcing. Interested individuals can contribute to a crowdsourcing task, essentially contributing towards the project's goals. To motivate participation and engagement, scientists use a variety of reward mechanisms. The most common motivation, and the one that yields the fastest results, is monetary rewards. By using monetary, scientists address a wider audience to participate in the task. As the payment is below minimum wage for developed economies, users from developing countries are more eager to participate. In subjective tasks, or tasks that cannot be validated through a right or wrong type of validation, monetary incentives could contrast with the much needed quality of submissions. We perform a subjective crowdsourcing task, emotion annotation, and compare the quality of the answers from contributors of varying income levels, based on the Gross Domestic Product. The results indicate a different contribution process between contributors from varying GDP regions. Low income contributors, possibly driven by the monetary incentive, submit low quality answers at a higher pace, while high income contributors provide diverse answers at a slower pace. © IFIP International Federation for Information Processing 2019