Kälin Roland E, Glass Rainer
Neurovascular Research, Department of Neurosurgery, University Hospital, LMU Munich, 81377 Munich, Germany.
Walter Brendel Center of Experimental Medicine, Faculty of Medicine, LMU Munich, 81377 Munich, Germany.
Cancers (Basel). 2021 Aug 2;13(15):3899. doi: 10.3390/cancers13153899.
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM-expansion depends on a dense vascular network and, coherently, GBMs are highly angiogenic. However, new intratumoral blood vessels are often aberrant with consequences for blood-flow and vascular barrier function. Hence, the delivery of chemotherapeutics into GBM can be compromised. Furthermore, leaky vessels support edema-formation, which can result in severe neurological deficits. The secreted signaling peptide Apelin (APLN) plays an important role in the formation of GBM blood vessels. Both APLN and the Apelin receptor (APLNR) are upregulated in GBM cells and control tumor cell invasiveness. Here we summarize the current evidence on the role of APLN/APLNR signaling during brain tumor pathology. We show that targeting APLN/APLNR can induce anti-angiogenic effects in GBM and simultaneously blunt GBM cell infiltration. In addition, we discuss how manipulation of APLN/APLNR signaling in GBM leads to the normalization of tumor vessels and thereby supports chemotherapy, reduces edema, and improves anti-tumorigenic immune reactions. Hence, therapeutic targeting of APLN/APLNR signaling offers an interesting option to address different pathological hallmarks of GBM.
胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的原发性脑肿瘤。GBM的生长依赖于密集的血管网络，相应地，GBM具有高度的血管生成能力。然而，肿瘤内新形成的血管往往异常，影响血流和血管屏障功能。因此，化疗药物向GBM的递送可能会受到影响。此外，渗漏的血管会促进水肿形成，进而导致严重的神经功能缺损。分泌型信号肽Apelin（APLN）在GBM血管形成中起重要作用。APLN及其受体（APLNR）在GBM细胞中均上调，并控制肿瘤细胞的侵袭性。在此，我们总结了目前关于APLN/APLNR信号在脑肿瘤病理过程中作用的证据。我们发现，靶向APLN/APLNR可在GBM中诱导抗血管生成作用，同时抑制GBM细胞浸润。此外，我们还讨论了在GBM中操纵APLN/APLNR信号如何导致肿瘤血管正常化，从而支持化疗、减轻水肿并改善抗肿瘤免疫反应。因此，对APLN/APLNR信号进行治疗性靶向为解决GBM的不同病理特征提供了一个有趣的选择。
