Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer.

Background And Aims: Fractalkine, a chemokine that presents as both a secreted and a membrane-anchored form, has been described as having tumour-suppressive activities in standard subcutaneous models. Here, we investigate the antitumour effect of fractalkine, in its three molecular forms, in two orthotopic models of metastatic colon cancer (liver and lung) and in the standard subcutaneous model.

Methods: We have developed models of skin tumours, liver and pulmonary metastasis and compared the extent of tumour development between C26 colon cancer cells expressing either the native, the soluble, the membrane-bound fractalkine or none.

Prostaglandin E2 induces interaction between hSlo potassium channel and Syk tyrosine kinase in osteosarcoma cells.

Prostaglandins (PGs) are important mediators of bone response to growth factors, hormones, inflammation, or mechanical strains. In this study, we show that in MG63 osteosarcoma cells, prostaglandin E2 (PGE2) produces the opening of a large conductance Ca2+-dependent K+ channel (BK). This PGE2-mediated channel opening induces the recruitment of various tyrosine-phosphorylated proteins on the hSlo alpha-subunit of BK.

Signal transduction pathways involved in soluble fractalkine-induced monocytic cell adhesion.

Fractalkine displays features that distinguishes it from the other chemokines. In particular, besides its chemoattractant action it promotes, under physiologic flow, the rapid capture and the firm adhesion of a subset of leukocytes or intervenes in the neuron/microglia interaction. This study verified that indeed the human monocytic MonoMac6 cell line adheres to fibronectin-coated filters in response to soluble fractalkine (s-FKN).

Arg777 plays a major role in the conformation of the colony-stimulating factor-1 receptor intracellular kinase domain.

A point mutation substituting Arg777 by Gln was obtained in a highly conserved region of the human colony-stimulating factor-1 receptor (CSF-1R) sequence. Constitutive expression of wild-type receptors in CHO cells confers susceptibility to CSF-1 for proliferation whereas the mutated receptors exhibited a 90% reduced efficiency in proliferation. We sought to determine the alterations intervening in the CSF-1 signal transduction of the Arg777Gln mutated receptor.

Extracellular ATP and UTP control the generation of reactive oxygen intermediates in human macrophages through the opening of a charybdotoxin-sensitive Ca2+-dependent K+ channel.

Human monocyte-derived macrophages possess a NADPH oxidase that catalyzes superoxide formation upon phagocytosis. Extracellular ATP per se does not activate NADPH oxidase but potentiates superoxide generation triggered by opsonized zymosan. UTP can substitute for ATP with the same efficiency, suggesting that ATP mediates its effects specifically through P2U receptors.