OBJECTIVE To evaluate the possible crosstalk between C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor 7 (CXCR7) axis with the mammalian target of rapamycin (mTOR) pathway in neuroendocrine tumors (NETs). METHODS Sixty-one human NETs were included into the study. CXCR4/CXCL12/CXCR7 axis and mTOR pathway were assessed by qRT-PCR and immunohistochemis...

CXCL12 is a pleiotropic chemokine capable of eliciting multiple signal transduction cascades and functions, via interaction with either CXCR4 or CXCR7. Factors that determine CXCL12 receptor preference, intracellular signalling route and biological response are poorly understood but are of central importance in the context of therapeutic intervention of the CXCL12 axis in multiple disease state...

Tissue migration is a collective behavior that plays a key role in the formation of many organ systems. Although tissue movements are guided by extrinsic cues, in many contexts, their receptors need to be active only at the leading edge to ensure morphogenesis. This has led to the prevalent view that extrinsic signals exert their influence by controlling a small number of leader cells. The zebr...

Chemokine CXCL12 and its two known receptors, CXCR4 and CXCR7, may play a role in diseases including tumor growth and metastasis, atherosclerosis, and HIV infection. Therefore, these molecules may be promising targets for drug development. While studies of cell signaling and high-throughput screening for drug discovery increasingly are based on luminescent assays because of their high sensitivi...

Cortical GABAergic interneurons have essential roles for information processing and their dysfunction is implicated in neuropsychiatric disorders. Transcriptional codes are elucidating mechanisms of interneuron specification in the MGE (a subcortical progenitor zone), which regulate their migration, integration, and function within cortical circuitry. Lhx6, a LIM-homeodomain transcription facto...

Primordial germ cell (PGC) migration in zebrafish is directed by the chemokine SDF-1a that activates its receptor CXCR4b. Guided PGC migration in zebrafish thus serves as a model for chemokinedirected cell migration, a process that is relevant for a wide range of events in development, homeostasis and disease. We show that during their migration PGCs generate bleb-like protrusions that are powe...

BACKGROUND The use of bone marrow-derived human multipotent stromal cells (hMSC) in cell-based therapies has dramatically increased in recent years, as researchers have exploited the ability of these cells to migrate to sites of tissue injury, inflammation, and tumors. Our group established that hMSC respond to "danger" signals--by-products of damaged, infected or inflamed tissues--via activati...

In liver injury, recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (sprocs) is necessary for normal liver regeneration. Hepatic vascular endothelial growth factor (VEGF) is a central regulator of the recruitment process. We examine whether stromal cell-derived factor 1 [sdf1, or CXC ligand 12 (CXCL12)] acts downstream from VEGF to mediate recruitment of BM sprocs...

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced change...

Chemokine stromal cell-derived factor-1 (SDF-1) and its receptors, CXCR4 and CXCR7, have been implicated in epithelial ovarian cancer progression and metastasis. However, limited data are available on the expression levels of SDF-1 and CXCR4 variants and CXCR7 in human epithelial ovarian cancer. The present study aimed to characterize the expression pattern and levels of SDF-1, CXCR4 and CXCR7 ...