Royston Daniel, Jackson David G
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
J Pathol. 2009 Apr;217(5):608-19. doi: 10.1002/path.2517.
The invasion of lymphatic vessels by colorectal cancer (CRC) and its subsequent spread to draining lymph nodes is a key determinant of prognosis in this common and frequently fatal malignancy. Although tumoural lymphangiogenesis is assumed to contribute to this process, review of the current literature fails to support any notion of a simple correlation between lymphatic vessel density and CRC metastasis. Furthermore, attempts to correlate the expression of various lymphangiogenic growth factors, most notably VEGF-C and VEGF-D, with the lymphatic metastasis of CRC have provided contradictory results. Recent evidence from animal and human models of tumour metastasis suggests that complex functional and biochemical interactions between the microvasculature of tumours and other cell types within the tumour microenvironment may play a pivotal role in the behaviour of commonly metastasizing tumours. Indeed, previous insights into tumoural blood vessels have provided candidate markers of tumoural angiogenesis that are currently the subject of intense investigation as future therapeutic targets. In this review article we survey the current evidence relating lymphangiogenesis and lymphangiogenic growth factor production to metastasis by CRC, and attempt to provide some insight into the apparent discrepancies within the literature. In particular, we also discuss some new and provocative insights into the properties of tumoural lymphatics suggesting that they have specific expression profiles distinct from those of normal lymphatic vessels and that appear to promote metastasis. These findings raise the exciting prospect of future biomarkers of lymphatic metastasis and identify potential targets for new generation anti-tumour therapies.
结直肠癌（CRC）对淋巴管的侵袭及其随后向引流淋巴结的扩散是这种常见且往往致命的恶性肿瘤预后的关键决定因素。尽管肿瘤淋巴管生成被认为促成了这一过程，但对当前文献的回顾未能支持淋巴管密度与结直肠癌转移之间存在简单关联的任何观点。此外，试图将各种淋巴管生成生长因子（最显著的是VEGF - C和VEGF - D）的表达与结直肠癌的淋巴转移相关联，结果相互矛盾。来自肿瘤转移动物模型和人类模型的最新证据表明，肿瘤微脉管系统与肿瘤微环境中其他细胞类型之间复杂的功能和生化相互作用，可能在常见转移肿瘤的行为中起关键作用。事实上，先前对肿瘤血管的深入了解提供了肿瘤血管生成的候选标志物，这些标志物目前是作为未来治疗靶点进行深入研究的对象。在这篇综述文章中，我们调查了当前将淋巴管生成和淋巴管生成生长因子产生与结直肠癌转移相关联的证据，并试图对文献中的明显差异提供一些见解。特别是，我们还讨论了一些关于肿瘤淋巴管特性的新的且具有启发性的见解，这些见解表明它们具有与正常淋巴管不同的特定表达谱，并且似乎促进转移。这些发现为未来淋巴转移生物标志物带来了令人兴奋的前景，并确定了新一代抗肿瘤治疗的潜在靶点。
