Basic Research: Sant’Anna School Life Sciences Institute researchers coordinated a new study published in Biochimica et Biophysica Acta journal on MICAL2 protein inhibition to stabilize solid tumors growth
A team of researchers from Pisa Sant’Anna School Life Sciences Institute, under the supervision of molecular biologist Debora Angeloni, have found that MICAL2 protein inhibition reduces endothelial cells viability and functions making them refractory to Vascular Endothelial Growth Factor (VEGF). The overall goal of this anti-angiogenic approach is to stabilize tumor growth through preventing the maturation of a functional vessel network, compromising the existing tumor-associated vasculature and inhibiting new vessel formation.
As basic research and clinical studies of solid tumors have raised serious concerns about the worthiness of anti-angiogenic drugs which showed little or temporary benefits to patients, a deeper understanding of the molecular distinctiveness of tumor blood vessels and identification of new therapeutic targets associated to neo-angiogenesis are needed. The study “MICAL2 is expressed in cancer associated neo-angiogenic capillary endothelia and it is required for endothelial cell viability, motility and VEGF response” published in “Biochimica et Biophysica Acta - Molecular Basis of Disease” journal, addressed the MICAL2 KD disabling endothelial cells response to VEGF.
Whole-genome gene expression profiling reveals MICAL2 involvement in angiogenesis and vascular development pathways. Based on these results, researchers proposed that MICAL2 expression participates to inflammation-induced neo-angiogenesis and that MICAL2 inhibition should be tested in cancer- and non-cancer-associated neo-angiogenesis, where chronic inflammation represents a relevant pathophysiological mechanism.
“Over the past decade, anti-angiogenic therapy has received considerable attention and is widely administered in several types of tumors. Nonetheless, there are potential consequences that decrease the efficiency of this therapy. We emphasized the need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors developing a new delivery system for the current inhibitors. MICAL-family proteins induce oxidation of actin molecules, leading to actin depolymerization. Actin is one protein that is affected by MICAL function, leading to cytoskeletal rearrangements. In this research, we highlighted the role of MICALs and their targets in cancer angiogenesis as have shown great promise for use in anti-metastatic cancer therapy. We also discussed the implications of these therapeutic strategies targeting angiogenesis as they are not used as single treatments but associated with standard chemotherapies”, said Angeloni.
The research developed by Debora Angeloni has been supported through public donations and the Lions Club International, Distretto 108LA, Toscana, financial contributions. “I would like to say how thankful we are for their generosity” – said Debora Angeloni. “Donations play an important role in accomplishing research tasks and medical discovery. We are working tirelessly to achieve them”.
Click here to download the paper.
Cover photo: expression of MICAL2 protein in ECs of neo-angiogenic capillaries branching off within the tumor mass of gastric and kidney carcinoma. In vivo angiogenesis shows an increased number of vascular structures with lumens and red blood cells (grey colour).
(source: paper co-author Debora Angeloni)
