Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche.

Unlabelled: Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill-defined. Here, we found that the vascular ETS-related gene (ERG) is a generalized mechanism regulating PMN activity in preclinical tissue injury models and human patients.

Evidence for reprogramming of monocytes into reparative alveolar macrophages in vivo by targeting PDE4b.

Increased lung vascular permeability and neutrophilic inflammation are hallmarks of acute lung injury. Alveolar macrophages (AMϕ), the predominant sentinel cell type in the airspace, die in massive numbers while fending off pathogens. Recent studies indicate that the AMϕ pool is replenished by airspace-recruited monocytes, but the mechanisms instructing the conversion of recruited monocytes into reparative AMϕ remain elusive.

Programming to S1PR1 Endothelial Cells Promotes Restoration of Vascular Integrity.

[Figure: see text].

S1PR1 and VEGFR2 - a synergy that promotes tumor angiogenesis?

We have recently uncovered that endothelial cell (EC) S1PR1 controls the effectiveness of VEGFR2 driven tumor angiogenesis. By using tumor ECs, EC-S1PR1 mice and S1PR1 antagonist, we showed that VEGF-VEGFR2 pathway requires EC-S1PR1-induced signaling to efficiently drive tumor vascularization and growth, indicating combining S1PR1 antagonist with anti-VEGF/VEGFR2 therapy may eradicate resistant tumors.

SPHK2-Generated S1P in CD11b Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages.

Acute lung injury (ALI) is a lethal inflammatory lung disorder whose incidence is on the rise. Alveolar macrophages normally act to resolve inflammation, but when dysregulated they can provoke ALI. We demonstrate that monocyte-derived macrophages (CD11b macrophages) recruited into the airspace upregulate the anti-inflammatory function of alveolar macrophages by suppressing their stimulator of type 1 interferon gene (STING) signaling.

Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling.

The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in endothelial cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic signaling to enhance tumor growth. We show that cancer cells induce S1PR1 activity in ECs, and thereby, conditional deletion of S1PR1 in ECs (EC-S1pr1 mice) impairs tumor vascularization and growth.

Aggressive serous epithelial ovarian cancer is potentially propagated by EpCAMCD45 phenotype.

Epithelial ovarian carcinoma (EOC) patients often acquire resistance against common chemotherapeutic drugs like paclitaxel and cisplatin. The mechanism responsible for the same is ambiguous. We have identified a putative drug-resistant tumour cell phenotype (EpCAMCD45) in the ascitic fluid of EOC patients, which appears to originate from the primary tumour.

Triplex forming oligonucleotides targeted to hmga1 selectively inhibit its expression and induce apoptosis in human cervical cancer.

High-mobility group A1 (HMGA1) is a non-histone chromosomal protein, which is known as 'architectural' transcription factor that facilitates the assembly of 'enhanceosome.' Because of its elevated expression in a number of human malignancies, with barely minimal levels in healthy adults, HMGA1 is considered as potential 'tumor marker.' Therefore, we looked at the inhibition of hmga1 using anti-gene strategy, as an attractive therapeutic approach.

Molecular aspects on adriamycin interaction with hmga1 regulatory region and its inhibitory effect on HMGA1 expression in human cervical cancer.

High mobility group A1 (HMGA1), a non-histone chromosomal protein, is highly expressed in a wide range of human cancers including cervical, breast, and prostate cancers. Therefore, hmga1 gene is considered as an attractive potential target for anticancer drugs. We have chosen 27 bp DNA sequence from a regulatory region of hmga1 promoter and studied its interaction with adriamycin (ADM) and in vitro expression of HMGA1 in the presence of ADM in HeLa cell line.

Interaction of doxorubicin with a regulatory element of hmga1 and its in vitro anti-cancer activity associated with decreased HMGA1 expression.

High mobility group A1 (HMGA1) non-histone chromatin protein is known as an architectural transcription factor that regulates transcription of various genes. HMGA1 is highly expressed in almost all human cancers and considered as a potent tumor marker. Because of its association with cancers, hmga1 is considered as a critical target for anti-cancer drugs.