Tumor angiogenesis: initiation and targeting - therapeutic targeting of an FGF-binding protein, an angiogenic switch molecule, and indicator of early stages of gastrointestinal adenocarcinomas -.
Tumor angiogenesis: initiation and targeting - therapeutic targeting of an FGF-binding protein, an angiogenic switch molecule, and indicator of early stages of gastrointestinal adenocarcinomas -.
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DOI：
10.4143/crt.2006.38.4.189
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发表时间：
2006-12
期刊：
影响因子：
--
通讯作者：
E. Tassi;A. Wellstein
中科院分区：
文献类型：
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作者：
E. Tassi;A. Wellstein
肿瘤血管生成与人类肿瘤的开始以及向更侵袭性行为的进展有关。特别是，血管生成因子的活性对肿瘤进展至关重要。我们以前的特点是分泌的成纤维细胞生长因子结合蛋白（FGF-BP）作为伴侣分子，结合各种FGF，增强FGF介导的生化和生物学事件，重要的是肿瘤依赖性血管生成的一个关键限速因子。我们产生了靶向FGF-BP蛋白的单克隆抗体，并将其用作评估档案组织样本中胰腺癌和结直肠癌恶性进展期间FGF-BP表达频率和模式的工具。我们发现，FGF-BP在结肠直肠癌和胰腺癌的发生过程中显著上调。本文讨论了结直肠癌和胰腺癌发生和发展的关键遗传事件，特别关注血管生成和抗血管生成治疗的调节。我们认为，胰腺癌和结肠癌早期分泌的FGF-BP蛋白的上调可能使这种蛋白成为一种可能的血清标志物，表明存在高风险的癌前病变。此外，FGF-BP的生物活性被单克隆抗体中和，表明基于抗体的治疗靶向的潜力。
Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. In particular, the activity of angiogenic factors is crucial for tumor progression. We previously characterized a secreted fibroblast growth factor-binding protein (FGF-BP) as a chaperone molecule, which binds to various FGFs, enhances FGF-mediated biochemical and biologic events and importantly is a crucial rate-limiting factor for tumor-dependent angiogenesis. We generated monoclonal antibodies that target FGF-BP protein and used them as a tool to evaluate frequency and pattern of FGF-BP expression during the malignant progression of pancreas and colorectal carcinoma in archival tissue samples. We found that FGF-BP is dramatically upregulated during the initiation of colorectal and pancreatic adenocarcinoma. Crucial genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis and antiangiogenic therapies are discussed. We propose that the upregulation of the secreted FGF-BP protein during early phases of pancreas and colon cancer could make this protein a possible serum marker indicating the presence of high-risk premalignant lesions. Furthermore, the biological activity of FGF-BP is neutralized by monoclonal antibodies suggesting the potential for antibody-based therapeutic targeting.