Wnt3a Expression is Associated with MMP-9 Expression in Primary Tumor and Metastatic Site in Recurrent or Stage IV Colorectal Cancer

Abstract

Infantile hemangioma (IH), which is the most common tumor in infants, is a benign vascular neoplasm resulting from the abnormal proliferation of endothelial cells and pericytes. For nearly a century, researchers have noted that IH exhibits diverse and often dramatic clinical behaviors. On the one hand, most lesions pose no threat or potential for complication and resolve spontaneously without concern in most children with IH. On the other hand, approximately 10% of IHs are destructive, disfiguring and even vision-or life-threatening. Recent studies have provided some insight into the pathogenesis of these vascular tumors, leading to a better understanding of the biological features of IH and, in particular, indicating that during hemangioma neovascularization, two main pathogenic mechanisms prevail, angiogenesis and vasculogenesis. Both mechanisms have been linked to alterations in several important cellular signaling pathways. These pathways are of interest from a therapeutic perspective because targeting them may help to reverse, delay or prevent hemangioma neovascularization. In this review, we explore some of the major pathways implicated in IH, including the VEGF/VEGFR, Notch, β-adrenergic, Tie2/angiopoietins, PI3K/AKT/mTOR, HIF-α-mediated and PDGF/PDGF-R-β pathways. We focus on the role of these pathways in the pathogenesis of IH, how they are altered and the consequences of these abnormalities. In addition, we review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against some of these pathways.

Jagged1/Notch3 Signaling Modulates Hemangioma-Derived Pericyte Proliferation and Maturation

“…Interestingly, we did observe the induction of p27 kip1 following Notch stimulation of Hem-pericytes, further supporting the idea of cell-specific activation of Notch effector molecules [29].…”

“…We proceeded based on our previous supposition that the Notch pathway might also contribute to establishing two distinct subpopulations at different steps of angiogenesis in IHs, such as ECs versus pericytes [29,37,38]. We demonstrated that the Jagged1 level was increased in involuting IH tissues [15].…”

Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo

“…In the present study, we found that knockdown of IGF2R could significantly downregulate the expression of PCNA, Ki-67, Bcl-2, Cyclin D1 and E and upregulated the expression of Bax in HA cells and xenograft HA samples, suggesting that IGF2R may promote the development and progression of human HA via upregulation of PCNA, Ki-67, Bcl-2, Cyclin D1 and E expression and downregulation of Bax expression. More importantly, PI3K/AKT has been found to play a role in the development of HAs (20,21). Activation of the PI3K/AKT pathway promotes tumor growth and invasion through upregulation of the PCNA and Ki-67 expression (33), blocks cell apoptosis through decrease of the Bax/Bcl-2 ratio (34), and prompts cell cycle progression through upregulation of Cyclin D/E expression (35).…”

“…Many studies have demonstrated that the PI3K/AKT pathway is involved in regulating HA formation (20,21). Whether Lv-siIGF2R affects PI3K/AKT signaling transduction of PI3K/AKT needed to be explored.…”

Serum and tissue profile of VEGF and its receptors VGFR1/R2 in children with infantile hemangiomas on systemic propranolol treatment

“…We still do not understand the complex biology of its rapid proliferation and spontaneous regression. However, some light has been recently shed on signaling pathways involved in these processes such as VEGF/VEGFR, Notch, Tie2/Angiopoetin, HIF␣, PI3 K/Akt/mTOR, PDGF-B/PDGFR-beta and B-adrenergic [1][2][3]. Some of these tumors, especially in proliferating phase interfere physiological functions or * Corresponding author at: Sporna Str 36/50, 91-738 Lodz, Poland.…”