Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: Angiogenesis in chronic pancreatitis and in pancreatic cancer
Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: Angiogenesis in chronic pancreatitis and in pancreatic cancer
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DOI：
10.1097/00006676-199901000-00012
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发表时间：
1999-01-01
期刊：
影响因子：
2.9
通讯作者：
Izbicki, JR
中科院分区：
文献类型：
--
作者：
Kuehn, R;Lelkes, PI;Izbicki, JR
最近的流行病学证据表明，慢性胰腺炎（CP）患者发生胰腺癌（PCA）的风险增加。尽管这两种疾病有许多相似之处，但从CP进展到PCA的机制仍知之甚少。我们推测，血管生成增强可能在CP和PCA的病因学和组织病理学中起关键作用，从而形成癌前病变和癌之间的可能联系。在18例CP患者，10例PCA患者和18例对照患者的手术标本中，血管的绝对数量和相对血管密度在血管性血友病因子和PECAM-1（血小板/内皮细胞粘附分子-1）的内皮细胞免疫染色后进行了评估。此外，细胞粘附分子ICAM-1（细胞间粘附分子-1）和VCAM-1（血管细胞粘附分子-1）和VEGF（血管内皮生长因子）的表达进行了研究，在所有标本。CP和PCA均表现出高血管密度区域（“热点”）。PCA中这些区域的平均血管数为132.2 +/- 16.8/mm（2），CP中为99.2 +/- 7.4/mm（2）。对照组的平均血管计数为25.1 +/- 5.1。与对照组（8.0 +/- 0.8%）相比，PCA（41.3 +/- 3.5%）和CP（30.6 +/- 2.6%）的相对血管密度均增加。PCA的绝对血管计数和相对血管密度均显著高于CP（p < 0.05）。ICAM-1在CP和PCA中的表达在CP的导管细胞和癌细胞中可见增强。在对照组中，ICAM-1和VCAM-1仅在内皮细胞中以低水平表达。VCAM-1强表达于腺泡细胞以及导管细胞。在CP和PCA中，VEGF在CP的导管细胞以及癌细胞中强烈表达。我们首次发现CP和PCA的血管生成活性均增加。基于这项研究，我们认为，抗血管生成可能是一个新的目标，预防或治疗慢性胰腺疾病。
Recent epidemiologic evidence suggests that patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic carcinoma (PCA). In spite of numerous similarities in both diseases, mechanisms for progression from CP to PCA are poorly understood. We hypothesized that enhanced angiogenesis might play a pivotal role in the etiology and histopathology of both CP and PCA, and thus form a possible link between precancer and carcinoma. In surgical specimens of 18 patients with CP, 10 with PCA, and 18 controls, absolute numbers of blood vessels and relative blood vessel density were assessed after immunostaining of endothelial cells for von Willebrand factor and PECAM-1 (platelet/endothelial cell adhesion molecule-1). Furthermore, the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and of VEGF (vascular endothelial growth factor) was investigated in all specimens. Both CP and PCA exhibited areas of high vascular density ("hot spots"). The mean number of blood vessels in these areas in PCA was 132.2 +/- 16.8 per mm(2), and in CP, 99.2 +/- 7.4 per mm(2). The mean vessel count in controls was 25.1 +/- 5.1. Relative vessel density was increased in both PCA (41.3 +/- 3.5%) and CP (30.6 +/- 2.6%) versus controls (8.0 +/- 0.8%). Both absolute vessel count and relative vessel density were significantly higher (p < 0.05) in PCA than in CP. Enhanced expression of ICAM-1 in CP and PCA was seen in ductal cells in CP and cancer cells. In controls, ICAM-1 and VCAM-1 were expressed only at low levels in endothelial cells. VCAM-1 was strongly expressed in acinar cells as well as in ductal cells. In CP and PCA, VEGF was strongly expressed in ductal cells in CP as well as in cancer cells. We shaw for the first time that angiogenic activity is increased in both CP and PCA. Based on this study, we suggest that antiangiogenesis might be a novel target for prevention or therapy in chronic pancreatic diseases.