Montemagno Christopher, Luciano Frédéric, Pagès Gilles
LIA ROPSE, Laboratoire International Associé, Centre Scientifique de Monaco, Université Côte d'Azur, Nice, France.
Institute for Research on Cancer and Aging of Nice (IRCAN), Centre Antoine Lacassagne, University Côte d'Azur, CNRS UMR 7284, INSERM U1081, Nice, France.
Methods Mol Biol. 2022;2475:1-23. doi: 10.1007/978-1-0716-2217-9_1.
Many cancers can be cured by combining surgery with healthy margins, radiation therapy and chemotherapies. However, when the pathology becomes metastatic, cancers can be incurable. The best situation involves "chronicization" of the pathology even for several years. However, most of the time, patients die within a few months. To disseminate throughout the body, cancer cells must enter the vascular network and seed in another organ. However, during the initiation of cancer processes, the tumor is avascular. Later, the production of angiogenic factors causes tumor neovascularization and subsequent growth and spread, and the presence of blood and/or lymphatic vessels is associated with high grade tumors. Moreover, during tumor development, cancer cells enter lymphatic vessels and disseminate via the lymphatic network. Hence, blood and lymphatic vessels are considered as main routes of metastatic dissemination and cancer aggressiveness. Therefore, anti-angiogenic drugs entered in the therapeutic arsenal from 2004. Despite undeniable effects however, they are far from curative and only prolong survival by a few months.Recently, the concepts of angio/lymphangiogenesis were revisited by analyzing the role of blood and lymphatic vessels at the initiation steps of tumor development. During this period, cancer cells enter lymphatic vessels and activate immune cells within lymph nodes to initiate an antitumor immune response. Moreover, the presence of blood vessels at the proximity of the initial nodule allows immune cells to reach the tumor and eliminate cancer cells. Therefore, blood and lymphatic networks have a beneficial role during a defined time window. Considering only their detrimental effects is a concern. Hence, administration of anti-angio/lymphangiogenic therapies should be revisited to avoid the destruction of networks involved in antitumor immune response. This review mainly focuses on one of the main drivers of lymphangiogenesis, the VEGFC and its beneficial and pejorative roles according to the grade of aggressive tumors.
许多癌症可以通过手术切除足够的切缘组织、放射治疗和化疗相结合来治愈。然而，当病理检查显示癌症已发生转移时，通常就无法治愈了。最好的情况是癌症病情能够“慢性化”，即便持续数年。然而，大多数情况下，患者会在几个月内死亡。癌细胞要扩散至全身，必须进入血管网络并在另一个器官中着床。然而，在癌症发生初期，肿瘤是无血管的。后来，血管生成因子的产生导致肿瘤新生血管形成，进而促进肿瘤生长和扩散，而且血管和/或淋巴管的存在与高级别肿瘤相关。此外，在肿瘤发展过程中，癌细胞会进入淋巴管并通过淋巴网络扩散。因此，血管和淋巴管被视为转移扩散和癌症侵袭性的主要途径。所以，抗血管生成药物自2004年起被纳入治疗手段。尽管其效果不可否认，但远非治愈性药物，仅能将生存期延长几个月。最近，通过分析血管和淋巴管在肿瘤发展起始阶段的作用，血管生成/淋巴管生成的概念被重新审视。在此期间，癌细胞进入淋巴管并激活淋巴结内的免疫细胞以启动抗肿瘤免疫反应。此外，初始瘤结节附近血管的存在使免疫细胞能够到达肿瘤并清除癌细胞。因此，在特定的时间窗内，血管和淋巴网络具有有益作用。仅考虑它们的有害影响是一个问题。因此，应重新审视抗血管生成/淋巴管生成疗法的应用，以避免破坏参与抗肿瘤免疫反应的网络。本综述主要聚焦于淋巴管生成的主要驱动因素之一——血管内皮生长因子C（VEGFC），以及根据侵袭性肿瘤分级其有益和有害的作用。
