Abstract
Angiogenesis is a biological process that involves the formation of new blood vessels from the existing vasculature, and it plays a fundamental role in the development and progression of several types of cancer, including lung cancer. The angiopoietin/Tie2 ligand/receptor system orchestrates vascular integrity. In particular, Angiopoietin-1 activates the endothelial cell (EC)-specific receptor tyrosine kinase, Tie2, which is essential for preserving endothelial quiescence. On the other hand, Angiopoietin-2 acts as an inhibitor of the Angiopoietin-1/Tie2 signaling pathways, thus facilitating the destabilization of quiescent endothelium in cases of inflammation and cancer. Clinical studies have proven that high levels of Angiopoietin-2 indicate the development of non-small-cell lung carcinomas (NSCLC), while high levels of Angiopoietin-2 are strongly related to tumor angiogenesis, lymphangiogenesis, metastasis, and poor prognosis. Interestingly, the association of Angiopoietin-2 levels with the type of surgical approach makes Angiopoietin-2 a valuable factor in selecting the most suitable therapeutic strategy for lung cancer patients. The role of the Angiopoietin-1 and Angiopoietin-4 levels in NSCLC development requires further investigation. The present review focuses on the clinical impact of the Angiopoietin-1, Angiopoietin-2, and Angiopoietin-4 levels in patients diagnosed with NSCLC, emphasizing the interaction between them, and how they affect the development, progression, and metastasis of lung disease. Finally, it estimates the role of angiopoietins levels in the effective therapy of lung cancer patients.
Highlights
Lung cancer is a substantially invasive and promptly metastasizing type of cancer, with the five-year survival rate of the disease expected to reach approximately 16% [1]
The overexpression of Ang-2 in lung cancer tissue is linked with the severity and poor prognosis of lung disease, the increased levels of Ang-2 are highly associated with metastasis, facilitating the stratification of patients through the selection of individuals who have a higher risk for metastasis [24,51,63,64]
No further analyses have been conducted concerning the concentration of Ang-4 in lung cancer tissues, and no studies have focused on the evaluation of the Ang-4 serum levels in patients diagnosed with lung carcinoma in order to further elucidate the role of the corresponding angiopoietin in lung disease
Summary
Lung cancer is a substantially invasive and promptly metastasizing type of cancer, with the five-year survival rate of the disease expected to reach approximately 16% [1]. Several studies have implied that angiogenenesis plays a pivotal role in the development, spread, and metastatic dissemination in several types of cancers, including lung cancer [11,12,13,14]. The most widely known angiogenic factors are vascular endothelial growth factor (VEGF), VEGF receptors (VEGFRs), and angiopoietins [15]. Angiopoietin-1 (Ang-1) stimulates vessel stabilization and maturation, while its role in the development of cancer remains rather vague [22,23]. Angiopoietin-2 (Ang-2) is a proangiogenic factor that is expressed at low levels in normal tissues, and is extensively expressed in tumor endothelial cells. It has been estimated that predominantly Ang-2, in association with VEGF and other proangiogenic factors, triggers tumor angiogenesis [24,25]. The angiopoietin family, and mainly Ang-2, is another predominant angiogenic factor implicated in lung cancer. It describes the role of angiopoietins in the development of lung cancer, and examines the value of angiopoietins as prognostic/diagnostic tools, their significance after surgery, and their potential as a future therapeutic target
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