Angiogenic ability of human endothelial cells was decreased following senescence induction with hydrogen peroxide: possible role of vegfr-2/akt-1 signaling pathway.

BACKGROUND: Many attempts are used to discover mechanisms driving impaired angiogenesis in age-related diseases. Angiogenesis is highly regulated by different signaling pathways. Here, we investigated the angiogenesis potential of human endothelial cells (ECs) upon exposure to hydrogen peroxide (H2O2), a cellular senescent factor. RESULTS: Data showed that the wound healing rate of HUVECs decreased upon incubation with H2O2 (P < 0.05). LOX activity and NO production were decreased in H2O2 treated cells (P < 0.05). Expression of miR-126 and VEGFR-2 up-regulated, while expression of miR-373 and HSP-70 up = regulated in H2O2 -induced cells (P < 0.05). In addition, we found that protein levels of p-Akt-1, VCAM-1, MMP-9, and IL-6 decreased in treated cells (P < 0.05). CONCLUSIONS: Our data showed that H2O2 reduced the angiogenic response of HUVECs in vitro, which may be due to impairment of the VEGFR-2 signaling pathway.

Tumor-derived extracellular vesicles: The metastatic organotropism drivers.

The continuous growing, spreading, and metastasis of tumor cells depend on intercellular communication within cells resident in a tissue environment. Such communication is mediated through the secretion of particles from tumor cells and resident cells known as extracellular vesicles (EVs) within a microenvironment. EVs are a heterogeneous population of membranous vesicles released from tumor cells that transfer many types of active biomolecules to recipient cells and induce physiologic and phenotypic alterations in the tissue environment. Spreading the 'seeds' of metastasis needs the EVs that qualify the 'soil' at distant sites to promote the progress of arriving tumor cells. Growing evidence indicates that EVs have vital roles in tumorigenesis, including pre-metastatic niche formation and organotropic metastasis. These EVs mediate organotropic metastasis by modifying the pre-metastatic microenvironment through different pathways including induction of phenotypic alternation and differentiation of cells, enrolment of distinct supportive stromal cells, up-regulation of the expression of pro-inflammatory genes, and induction of immunosuppressive status. However, instead of pre-metastatic niche formation, evidence suggests that EVs may mediate reawakening of dormant niches. Findings regarding EVs function in tumor metastasis have led to growing interests in the interdisciplinary significance of EVs, including targeted therapy, cell-free therapy, drug-delivery system, and diagnostic biomarker. In this review, we discuss EVs-mediated pre-metastatic niche formation and organotropic metastasis in visceral such as lung, liver, brain, lymph node, and bone with a focus on associated signaling, causing visceral environment hospitable for metastatic cells. Furthermore, we present an overview of the possible therapeutic application of EVs in cancer management.