胆囊癌淋巴转移分子机制研究进展

胆囊癌是胆道系统常见的恶性肿瘤.影响胆囊癌手术预后的因素包括:侵袭深度,组织学分级,淋巴及周围神经浸润和淋巴结转移.淋巴转移是胆囊癌常见的转移方式,其分子机制目前仍不甚清楚.血管内皮生长因子-C (VEGF-C)/VEGF-D及其受体VEGFR-3能够促进淋巴管生成,在淋巴转移中起到重要作用；p16基因通过突变和甲基化,可能使肿瘤细胞恶性程度增加,与肿瘤的侵袭及淋巴结转移密切相关；缺氧诱导因子-1α(hypoxia inducible factor 1α,HIF-1α)可能通过诱导VEGF-C/-D的表达而调节肿瘤淋巴管生成,促进肿瘤淋巴结转移；细胞外基质(extracellular matrix,ECM)的降解是肿瘤细胞进入淋巴管的必要条件,基质金属蛋白酶(matrix metalloproteinase,MMPs)家族中MMP-2与MMP-9通过降解细胞外基质,为肿瘤细胞进入淋巴管提供必要条件,可能与胆囊癌淋巴转移有关.

Progress of the molecular mechanisms research of gallbladder cancer lymphatic metastasis

Gallbladder cancer(GBC) is the most frequent biliary tract malignancy.Prognostic factors that influence the success of aggressive surgical therapy include depth of invasion,histologic grade,lymphatic or perineural invasion,and lymphatic metastasis.Lymphatic metastasis is a common way of metastasis.The molecular mechanism of lymphatic metastasis remains unclear.VEGF-C/VEGF-D and its receptor VEGFR-3 promote Lymphangiogenesis and play a key role in lymph node metastasis.p16 may increase the degree of malignancy,through mutation and methylation,which is related to lymphatic metastasis.Hypoxia inducible factor 1α(HIF-1α) induces the expression of VEGF-C/-D,promote Lymphangiogenesis and lymph node metastasis.In the gene family of matrix metalloproteinase(MMPs),MMP-2 and MMP-9 may be associated with the lymphatic metastasis,which can degradate extracellular matrix(ECM).