Do any microcirculation changes reflect the malignant transformation in the intestinal tract during the multistep carcinogenesis?

Apc^（Min/+）小鼠为自发性腺瘤性息肉病和随后的癌的发展提供了一种独特的原位模型，称为腺瘤-癌序列。在目前的研究中，我们试图通过肠上皮肿瘤模型的形态学特征来阐明肿瘤血管生成模式与肿瘤转化顺序之间的关系。我们发现良性肿瘤的血管结构异常和血管生成模式与恶性肿瘤相似。在腺瘤-癌序列的早期阶段，在小鼠和人类的肿瘤前肠病变中，一些血管生成标记物，如VEGF都过表达。一种新的内在血管生成因子，血管hibin-2蛋白在腺癌原位肿瘤血管周围被检测到，但在Apc^（Min/+）肿瘤的早期腺瘤中不存在。这些结果表明，局部血管网的恶性变化早于肠上皮的恶性转化。因此，我们认为肿瘤前腺瘤性息肉病的微血管变化可能是肠腺癌进展的重要诊断标志，可能有助于预测肿瘤由良性向恶性转变

Apc^(Min/+) mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, termed the adenoma-carcinoma sequence. In the current study, we sought to clarify the relationship between the patterns of tumor angiogenesis and the sequence of neoplastic transformation in intestinal epithelia, by the morphological characterization of this tumor models. We found that structural abnormalities of tumor vessels and the pattern of tumor angiogenesis in benign tumors resembled that in malignant tumors. Several angiogenic markers, such as VEGF were overexpressed in pre-neoplastic intestinal lesions from very early stages during the adenoma-carcinoma sequence in both mice and humans. A novel intrinsic angiogenic factor, Vasohibin-2 protein was detected around tumor blood vessels in adenocarcinomas in situ, but was absent from adenomas during early stages of Apc^(Min/+) tumors. These results indicated that malignant changes in local vascular networks occurred earlier than malignant transformation of the intestinal epithelia. Therefore, we suggest that microvascular changes in preneoplastic adenomatous polyposis may be an important diagnostic sign for the progression of intestinal adenocarcinoma and may be useful to predict the transformation of tumors from a benign to a malignant state