VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression
VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression
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DOI：
10.1038/sj.neo.7900186
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发表时间：
2001-09-01
期刊：
影响因子：
4.8
通讯作者：
Swift, RI
中科院分区：
文献类型：
--
作者：
George, ML;Tutton, MG;Swift, RI
我们的目的是评估血管生成细胞因子VEGF-A、VEGF-C和VEGF-D及其受体VEGFR-2和VEGFR-3在腺瘤-癌序列和结直肠癌（CRC）转移扩散中的关系。采用半定量逆转录聚合酶链反应检测70例结直肠癌（35例伴配对粘膜）和20例腺瘤性息肉的mRNA表达水平。免疫组织化学和ELISA评估蛋白表达。与正常粘膜相比，息肉和CRC中VEGF-D mRNA表达显著降低（分别为P=.0002和.002），而VEGF-A和VEGF-C在CRC中显著升高（分别为P=.006和.004），但息肉中无此现象（分别为P=.22和P=.5）。受体在肿瘤组织和正常粘膜中的表达相似。与非转移性肿瘤相比，有淋巴结转移的肿瘤具有显著更高的VEGF-A水平（P= 0.043）。VEGF-C或VEGF-D与淋巴扩散之间无相关性。在息肉和癌中发生的VEGF-D的减少可能允许更高水平的VEGF-A和VEGF-C更容易结合VEGF受体，并产生肿瘤生长所需的血管生成开关。VEGF-A在CRC中的表达增加与淋巴转移有关，因此，VEGF家族的这个成员可能是决定转移扩散的最重要因素。
We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carcinoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA expression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenomatous polyps. Immuohistochemistry and ELISA assessed protein expression. VEGF-D mRNA expression was significantly lower in both polyps and CRCs compared with normal mucosa (P=.0002 and .002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and .004, respectively), but not polyps (P=.22 and P=.5, respectively). Receptor expression was similar in tumor tissue and normal mucosae. Tumors with lymph node metastases had significantly higher levels of VEGF-A compared with non-metastatic tumors (P=.043). There was no association between VEGF-C or VEGF-D and lymphatic spread. The decrease in VEGF-D occurring in polyps and carcinomas may allow the higher levels of VEGF-A and VEGF-C to bind more readily to the VEGF receptors, and produce the angiogenic switch required for tumor growth. Increased expression of VEGF-A within CRCs was associated with lymphatic metastases, and therefore, this member of the VEGF family may be the most important in determining metastatic spread.