At sub-lethal conditions, cell migration, a key step in angiogenesis turned out to be inhibited in a tumor-selective manner along with actin cytoskeleton disorganization on hemangioma cells.
Platelet-derived growth factor R-β (PDGFR-β), CD133, and peroxisome-proliferator-activated receptor gamma (PPAR-γ) were selected as the markers to observe MSCs in hemangioma by immunohistochemistry staining, with costaining of CD31 and alpha-smooth muscle actin (α-SMA).
These hemangioma-derived MSCs (Hem-MSCs) are similar to MSCs obtained from human bone marrow, expressing the cell surface markers SH2 (CD105), SH3, SH4, CD90, CD29, smooth muscle alpha-actin, and CD133 but not the hematopoietic markers CD45 and CD14 or the hematopoietic/endothelial markers CD34, CD31, and kinase insert domain receptor (KDR).
An antibody against a universal proliferation marker, Ki-67, detected nonproliferative, single-layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma. alpha-actin staining (antibody against perivascular tissue such as smooth muscle cells (SMCs) and/or pericytes) demonstrated that pathologic vessels lost their surrounding supportive tissues, as was previously seen in other types of vascular anomaly.
To the best of the authors' knowledge, >120 mutations in ADAR1 have been reported to cause DSH; however, no previous studies have reported mutations in ADAR1 in DSH at birth, with CHD and hemangioma.
We have also shown using our in vitro explant model that the cells emanating from proliferating haemangioma biopsies form blast-like structures that proliferate in the presence of angiotensin II.
Furthermore, the subtle regulation of allograft inflammatory factor-1 in the involution of hemangiomas will help design a new anti-angiogenic therapy for some tumors.
The expression of AKT, mTOR and proliferating cell nuclear antigen (PCNA) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA.
Disruption and inactivation of the PP2A complex promotes the proliferation and angiogenesis of hemangioma endothelial cells through activating AKT and ERK.
Using immunohistochemistry assay, we examined the expression levels of VEGF, VEGFR2, Ki-67, glucose transporter-1 (Glut-1), phosphorylated protein kinase B (p-AKT) and p-ERK in different phases of human HAs.
Furthermore, MEG3 was verified to act as a sponge of miR-494 in HAs cells, and miR-494 counteracted MEG3-caused anti-proliferative effects by regulating PTEN/PI3K/AKT pathway, and exhibited the negative correlation with MEG3 and PTEN expression in proliferating phase HAs.
Taken together, our findings demonstrate that HMGB1 may be implicated in the formation of HA through upregulation of AKT pathway, and represent a potential therapeutic target for treating HA.
In conclusion, propranolol inhibited proliferation and induced apoptosis of HemECs via Akt pathway by down-regulating Ang-2 expression, which contributes to our understanding on the pathogenesis of hemangioma and promotes the development of therapeutic approaches for hemangioma.
Using real-time PCR, the level of AKT1 was much higher in hemangioma group, whereas level of AKT3 was much lower in the hemangioma group, and in general expression level of ATK was upregulated in the hemangioma group.
In conclusion, knockdown of ID-1 suppressed proliferation and promoted apoptosis by inactivating phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling in HDECs, shedding light on the function of ID-1 in HA progression and highlighting the therapeutic value of ID-1 for HA.
Using real-time PCR, the level of AKT1 was much higher in hemangioma group, whereas level of AKT3 was much lower in the hemangioma group, and in general expression level of ATK was upregulated in the hemangioma group.
The authors report for the first time that angiogenin may be a useful serum marker for hemangiomas, and report a novel analysis process that might efficiently screen for potential serum markers of tumors by cDNA microarray analysis.
We found Tie2 mRNA and protein up-regulated with a concomitant increase in cellular responsiveness to Ang1 in most hemangioma-derived endothelial cells.
Ang2 mRNA was down-regulated in response to serum in hemangioma-derived endothelial cells, but not in normal endothelial cells, suggesting altered regulation.
In conclusion, propranolol inhibited proliferation and induced apoptosis of HemECs via Akt pathway by down-regulating Ang-2 expression, which contributes to our understanding on the pathogenesis of hemangioma and promotes the development of therapeutic approaches for hemangioma.