Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA.
Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA.
Cell Oncol (Dordr). 2019 Aug;42(4):423-447. doi: 10.1007/s13402-019-00447-x. Epub 2019 Apr 16.
Caveolin-1 (cav-1) is the major structural protein of caveolae, the flask-shaped invaginations of the plasma membrane mainly involved in cell signaling. Today, cav-1 is believed to play a role in a variety of disease processes including cancer, owing to the variations of its expression in association with tumor progression, invasive behavior, metastasis and therapy resistance. Since first detected in the brain, a number of studies has particularly focused on the role of cav-1 in the various steps of brain tumorigenesis. In this review, we discuss the different roles of cav-1 and its contributions to the molecular mechanisms underlying the pathobiology and natural behavior of brain tumors including glial, non-glial and metastatic subtypes. These contributions could be attributed to its co-localization with important players in tumorigenesis within the lipid-enriched domains of the plasma membrane. In that regard, the ability of cav-1 to interact with various cell signaling molecules as well as the impact of caveolae depletion on important pathways acting in brain tumor pathogenesis are noteworthy. We also discuss conversant causes hampering the treatment of malignant glial tumors such as limited transport of chemotherapeutics across the blood tumor barrier and resistance to chemoradiotherapy, by focusing on the molecular fundamentals involving cav-1 participation.
Cav-1 has the potential to pivot the molecular basis underlying the pathobiology of brain tumors, particularly the malignant glial subtype. In addition, the regulatory effect of cav-1-dependent and caveola-mediated transcellular transport on the permeability of the blood tumor barrier could be of benefit to overcome the restricted transport across brain barriers when applying chemotherapeutics. The association of cav-1 with tumors of the brain other than malignant gliomas deserves to be underlined, as well given the evidence suggesting its potential in predicting tumor grade and recurrence rates together with determining patient prognosis in oligodendrogliomas, ependymomas, meningiomas, vestibular schwannomas and brain metastases.
窖蛋白-1（cav-1）是质膜凹陷囊泡（主要参与细胞信号转导）的主要结构蛋白。如今，由于 cav-1 的表达变化与肿瘤进展、侵袭行为、转移和治疗耐药性相关，人们认为它在包括癌症在内的各种疾病过程中发挥作用。自从首次在大脑中检测到以来，许多研究特别关注 cav-1 在脑肿瘤发生的各个步骤中的作用。在这篇综述中，我们讨论了 cav-1 的不同作用及其对脑肿瘤包括神经胶质、非神经胶质和转移性亚型的病理生物学和自然行为的分子机制的贡献。这些贡献可能归因于其与质膜富含脂质区域内肿瘤发生的重要参与者的共定位。在这方面，cav-1 与各种细胞信号分子相互作用的能力以及 Cav-1 耗竭对脑肿瘤发病机制中重要途径的影响值得注意。我们还讨论了阻碍恶性神经胶质瘤等治疗的相关原因，例如化疗药物通过血脑肿瘤屏障的转运受限以及对放化疗的耐药性，重点关注涉及 cav-1 参与的分子基础。
cav-1 有可能成为脑肿瘤病理生物学基础的关键分子，特别是恶性神经胶质亚型。此外，cav-1 依赖性和 Cav-1 介导的跨细胞转运对血脑肿瘤屏障通透性的调节作用可能有助于克服在应用化疗药物时穿过脑屏障的受限转运。cav-1 与脑肿瘤的关联，除了恶性神经胶质瘤外，也值得强调，因为有证据表明其在预测肿瘤分级和复发率以及确定少突胶质细胞瘤、室管膜瘤、脑膜瘤、前庭神经鞘瘤和脑转移瘤患者的预后方面具有潜在作用。
