Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.
作者： David J. McConkey , Roy S. Herbst , Hiroki Kuniyasu , Corazon D. Bucana , Hisashi Shinohara
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摘要: We investigated the molecular mechanisms of angiogenesis in experimental brain metastasis. Cells from six different human cancer cell lines (proven to produce visceral metastasis) were injected into internal carotid artery nude mice. Colon carcinoma (KM12SM) and lung adenocarcinoma (PC14PE6 PC14Br) cells produced large, fast-growing parenchymal brain metastases, whereas lung squamous carcinoma (H226), renal (SN12PM6), melanoma (TXM13) cells produced only a few slow-growing metastases. Rapidly progressing brain metastases contained many enlarged blood vessels. The expression of VEGF mRNA protein by tumor directly correlated with angiogenesis growth Causal evidence for the essential role this process was provided transfecting PC14PE6 KM12SM with antisense- VEGF165 gene, which significantly decreased incidence brain metastasis. In contrast, transfection H226 squamous carcinoma sense-VEGF121 or sense-VEGF165 neither enhanced nor inhibited formation Collectively, results indicate that expression is necessary but not sufficient the production metastasis inhibition VEGF represents an important therapeutic target.
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