Carvalho T, Elias A P, Nunes T, Peleteiro M C, Dias S
Centro de Investigação Interdisciplinar em Sanidade Animal , Faculdade de Medicina Veterinária, TUL, Lisboa, Portugal.
Vet Immunol Immunopathol. 2008 Feb 15;121(3-4):344-58. doi: 10.1016/j.vetimm.2007.09.020. Epub 2007 Oct 10.
Angiogenesis and inflammation are two processes regulated by numerous common molecular mechanisms. Inflammation can stimulate angiogenesis, and angiogenesis can facilitate inflammation; both mechanisms have been shown to be involved in carcinogenesis. With this study we sought to gain an understanding of the molecular mechanisms involved in tumor angiogenesis and inflammation in urinary bladder tumors. Tumor specimens were collected at slaughter from Friesian cows chronically exposed to bracken fern. Bracken chronic toxicity is characterized by the presence of multiple mixed tumors in the bladder, being reported throughout the world under the designation of bovine enzootic hematuria. We conducted molecular analyses of angiogenic factors and chemokine production by real-time RT-PCR, and also assessed microvessel density (MVD), microvessel pericyte coverage index (MPI) to reveal mature vessels, the extent of tumor-infiltrating leukocytes (TILk) and tumor cell apoptosis and proliferation in both epithelial and endothelial-derived bovine urinary bladder tumors. We defined a profile of chemokines/chemokine receptors (Mip1beta, CCR1) and angiogenesis-related factors (VEGF, VEGFR2) that allow distinguishing between urothelial carcinomas (epithelial origin) and hemangiosarcomas (endothelial origin). Taken together, our data reveals previously unrecognized paracrine and autocrine chemo-angiogenic loops in the context of bovine urinary bladder tumorigenesis.
血管生成和炎症是由众多共同分子机制调节的两个过程。炎症可刺激血管生成，而血管生成又可促进炎症；这两种机制均已被证明参与致癌过程。通过本研究，我们试图了解膀胱肿瘤中肿瘤血管生成和炎症所涉及的分子机制。在屠宰时收集长期接触蕨菜的弗里斯兰奶牛的肿瘤标本。蕨菜慢性毒性的特征是膀胱中存在多个混合肿瘤，在世界各地以牛地方流行性血尿的名称报道。我们通过实时逆转录聚合酶链反应对血管生成因子和趋化因子的产生进行了分子分析，还评估了微血管密度（MVD）、微血管周细胞覆盖指数（MPI）以揭示成熟血管、肿瘤浸润白细胞（TILk）的程度以及上皮和内皮来源的牛膀胱肿瘤中肿瘤细胞的凋亡和增殖情况。我们确定了趋化因子/趋化因子受体（Mip1β、CCR1）和血管生成相关因子（VEGF、VEGFR2）的特征，这些特征有助于区分尿路上皮癌（上皮起源）和血管肉瘤（内皮起源）。综上所述，我们的数据揭示了在牛膀胱肿瘤发生过程中以前未被认识的旁分泌和自分泌化学血管生成环。
