Heissig Beate, Salama Yousef, Takahashi Satoshi, Okumura Ko, Hattori Koichi
Department of Immunological Diagnosis, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine.
Cancers (Basel). 2021 Mar 1;13(5):1014. doi: 10.3390/cancers13051014.
Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and cancer growth. Endothelial cells release growth factors such as epidermal growth factor-like protein-7 (EGFL7), which contributes to the formation of the tumor vasculature. The signaling axis formed by EGFL7 and one of its receptors, beta 3 integrin, has emerged as a key mediator in the regulation of tumor metastasis and drug resistance. Here we summarize recent studies on the role of the ECM-linked angiocrine factor EGFL7 in primary tumor growth, neoangiogenesis, tumor metastasis by enhancing epithelial-mesenchymal transition, alterations in ECM rigidity, and drug resistance. We discuss its role in cellular adhesion and migration, vascular leakiness, and the anti-cancer response and provide background on its transcriptional regulation. Finally, we discuss its potential as a drug target as an anti-cancer strategy.
癌细胞侵袭周围组织和脉管系统是肿瘤进展及远处转移形成的重要步骤。细胞外基质(ECM)是许多支持新血管形成和癌症生长的生物分子的所在之处。内皮细胞释放诸如表皮生长因子样蛋白-7(EGFL7)等生长因子,其有助于肿瘤脉管系统的形成。由EGFL7及其受体之一β3整合素形成的信号轴已成为肿瘤转移和耐药性调控中的关键介质。在此,我们总结了近期关于细胞外基质相关血管分泌因子EGFL7在原发性肿瘤生长、新生血管生成、通过增强上皮-间质转化促进肿瘤转移、细胞外基质硬度改变及耐药性方面作用的研究。我们讨论了其在细胞黏附与迁移、血管渗漏及抗癌反应中的作用,并提供了其转录调控的背景信息。最后,我们探讨了其作为抗癌策略药物靶点的潜力。