AdipoRon promotes angiogenesis in B-cell leukemia by modulating pro-angiogenic factors through AdipoR1

Background: Adiponectin, a cytokine predominantly secreted by adipose tissue, is increasingly recognized for its role in cancer, including hematologic malignancies. However, its involvement in leukemia-related angiogenesis remains poorly understood. Here, we investigated the effects of AdipoRon, an adiponectin agonist, on angiogenesis in the JVM-2 lymphoblastic cell line, a model for B-cell leukemia. Methods: The effects of AdipoRon were assessed on human umbilical vein endothelial cells (HUVECs) and JVM-2 cells using the tube formation assay. The expression of VEGF receptors, VEGF-A, HIF-1α, and CXCL-1 were investigated at both mRNA by quantitative real-time PCR and protein levels by ELISA and Western Blotting. The role of AdipoR1 and AdipoR2 in mediating AdipoRon effects was investigated by siRNA-mediated silencing of each receptor. Results: AdipoRon significantly promoted angiogenesis in HUVECs, both directly and through the secretion of soluble factors from JVM-2 cells. Treatment with AdipoRon upregulated VEGF-A and its receptors, with VEGF-R2 showing the most prominent increase. Additionally, both HIF-1α and CXCL-1 were up-regulated following AdipoRon administration. Finally, silencing of AdipoR1, but not AdipoR2, diminishes the AdipoRon-induced upregulation of the angiogenesis-related factors, suggesting that AdipoR1 is the primary receptor mediating the effects of adiponectin in leukemia cells. Conclusion: Our findings demonstrated that AdipoRon promotes angiogenesis in B-cell leukemia by enhancing pro-angiogenic factors through AdipoR1highlighting adiponectin’s significance in angiogenesis. A better understanding of adiponectin’s mechanisms could facilitate the development of therapeutic strategies targeting its pathway to inhibit tumor angiogenesis, offering promising approaches for leukemia treatment. Further studies are needed to fully explore adiponectin potential in leukemia.