Ohhashi T
First Department of Physiology, Shinshu University School of Medicine, Japan.
Nihon Geka Gakkai Zasshi. 2001 Jun;102(6):435-9.
Carcinoma frequently spreads and grows through the lymphatic system, whereas malignant tumors of mesenchymal origin more frequently spread via the hematogenous route. This paper reviews cancer spread with special reference to tumor microcirculation, vascular endothelial growth factor receptor (VEGFR)-3-mediated lymphangiogenesis, regeneration of collecting lymph vessels, and the role of nitric oxide in lymphatic metastasis. Oxygen and pH are key microenvironmental factors in the development and growth of tumors and their response to treatment. Thus the physiological and pathophysiological roles of hypoxia and acidic pH in the tumor microenvironment in lymphatic metastasis are demonstrated. Lymph angiogenesis in tumor tissues and regeneration of collecting lymph vessels with special reference to VEGFR-3 and its agonists VEGF-C/VEGF-D are discussed. The occurrence and biological significance of intratumoral lymph angiogenesis in breast cancer have been established. VEGF-C as a molecular link between tumor lymph angiogenesis and metastasis is identified. Finally, the role of nitric oxide (NO) in tumor microcirculation and lymphatic metastasis of carcinoma cells is evaluated.
癌常常通过淋巴系统扩散和生长，而间充质起源的恶性肿瘤则更常通过血行途径扩散。本文回顾了癌症的扩散，特别提及肿瘤微循环、血管内皮生长因子受体（VEGFR）-3介导的淋巴管生成、集合淋巴管的再生以及一氧化氮在淋巴转移中的作用。氧气和pH值是肿瘤发生发展及其对治疗反应的关键微环境因素。因此，本文证明了缺氧和酸性pH值在肿瘤微环境中对淋巴转移的生理和病理生理作用。本文讨论了肿瘤组织中的淋巴管生成以及集合淋巴管的再生，特别提及VEGFR-3及其激动剂VEGF-C/VEGF-D。乳腺癌肿瘤内淋巴管生成的发生及其生物学意义已得到证实。VEGF-C被确定为肿瘤淋巴管生成与转移之间的分子联系。最后，评估了一氧化氮（NO）在肿瘤微循环和癌细胞淋巴转移中的作用。
