Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.
Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.
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DOI：
10.1038/sj.bjc.6603839
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发表时间：
2007-07-16
影响因子：
8.8
通讯作者：
Bates, D. O.
中科院分区：
文献类型：
--
作者：
Pritchard-Jones, R. O.;Dunn, D. B. A.;Qiu, Y.;Varey, A. H. R.;Orlando, A.;Rigby, H.;Harper, S. J.;Bates, D. O.
恶性黑色素瘤是最致命的皮肤癌，在英国发病率的上升速度比任何其他癌症都要快。血管新生——从先前存在的血管系统中生长出新的血管——是肿瘤存活和发展的绝对必要条件，肿瘤的直径超过几百微米。我们之前描述了一类VEGF的抗血管生成异构体VEGFxxxb，在动物模型中抑制肿瘤生长，并且在某些癌症中下调，但尚未在黑色素瘤中进行研究。为了确定VEGFxxxb在黑色素瘤中的表达是否改变，我们使用了PCR和存档的人类肿瘤样本的免疫组织化学。在正常表皮和部分黑色素瘤样本中，可见VEGFxxxb染色。一些黑色素瘤的染色较弱。随后的检查显示，与未发生肿瘤转移的患者相比，随后发生肿瘤转移的患者的原发性黑色素瘤样本（水平和垂直生长阶段）的表达显著降低（方差分析（ANOVA） P<0.001，转移性与非转移性），而与肿瘤厚度无关，而周围表皮的表达没有差异。VEGF在转移性、非转移性黑色素瘤和正常表皮中均有表达。VEGFxxxb表达缺失似乎可以预测原发性黑色素瘤患者的转移性扩散。这些结果表明，剪接作为转移过程的一部分，存在从抗血管生成到促血管生成的VEGF亚型的转换。这可能是更广泛的转移剪接表型的一部分。
Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis – the growth of new vessels from preexisting vasculature – is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGFxxxb, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma. To determine whether VEGFxxxb expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGFxxxb staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) P<0.001 metastatic vs nonmetastatic), irrespective of tumour thickness, while the surrounding epidermis showed no difference in expression. Staining for total VEGF expression showed staining in metastatic and nonmetastatic melanomas, and normal epidermis. An absence of VEGFxxxb expression appears to predict metastatic spread in patients with primary melanoma. These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.
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DOI：
10.1007/s00432-003-0509-8
发表时间：
2004-02-01
影响因子：
3.6
作者：
Potti, A;Moazzam, N;Kargas, S
通讯作者：
Kargas, S
影响因子：
8
作者：
Shields, J. D.;Emmett, M. S.;Bates, D. O.
通讯作者：
Bates, D. O.
影响因子：
9
作者：
BRESLOW, A
通讯作者：
BRESLOW, A
影响因子：
56.9
作者：
SENGER, DR;GALLI, SJ;DVORAK, HF
通讯作者：
DVORAK, HF
影响因子：
7.5
作者：
Dadras, SS;Lange-Asschenfeldt, B;Detmar, M
通讯作者：
Detmar, M