Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis

Abstract

Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.

Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival

“…A growing body of evidence shows that the therapeutic efficacy of MSCs in MI is largely attributed to their paracrine effects, especially their angiogenic capacity. Interestingly, Apelin mediates cellular angiogenesis via multiple pathways [ 43 , 44 ]. We also found that Apelin-13 pretreatment greatly enhanced the angiogenic capacity of MSCs, as evidenced by the increased capillary-like tube formation of HUVECs cultured with conditioned medium and enhanced capillary and arteriole density in the ischemic heart tissue.…”

Roles of apelin/APJ system in cancer: Biomarker, predictor, and emerging therapeutic target

“…As a new lymphangiogenesis factor, apelin may have potential clinical research value for a new type of antitumor therapy targeting lymphangiogenesis (Berta et al, 2014). Apelin can promote the lymph vascularization of skin melanoma and the growth of lung metastases (Berta et al, 2021). High apelin levels can be used as a diagnostic indicator for MM, which has excellent clinical diagnostic value for MM (Maden et al, 2016).…”

Melanoma Progression under Obesity: Focus on Adipokines

“…Next, research revealed that, also, apelin overexpression increased the number and size of melanoma lung metastases in mice. Additionally, in vitro studies showed that higher apelin expression enhances the migratory and invasive abilities of melanoma cell lines, but does not influence their proliferation [132]. However, the inhibition of miR-4286 altered the mRNA expression of, among others, this hormone gene that next was implicated in the regulation of melanoma cell proliferation and apoptosis [200].…”

“…However, the inhibition of miR-4286 altered the mRNA expression of, among others, this hormone gene that next was implicated in the regulation of melanoma cell proliferation and apoptosis [200]. Interestingly, apelin and VEGF plasma concentrations were more elevated in patients with melanoma than in healthy individuals [132].…”