Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma
Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma
复制标题
DOI：
10.1136/jcp.2003.014498
复制
发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Campani, D
中科院分区：
文献类型：
--
作者：
Esposito, I;Menicagli, M;Campani, D
背景：炎症细胞通过产生增强肿瘤侵袭性的分子，促进人类恶性肿瘤的生长和扩散。目的：表征胰腺导管腺癌中的炎症浸润，并分析其对血管生成的贡献及其预后相关性。方法：采用免疫组织化学方法鉴定炎症细胞，并评估 137 例胰腺癌炎症细胞和癌细胞中促血管生成和前淋巴管生成分子（血管内皮生长因子 A (VEGF-A)、VEGF-C 和碱性成纤维细胞生长因子 (bFGF)）的表达。使用CD34作为内皮细胞标记物评估瘤内微血管密度（IMD）。结果：胰腺癌中的肥大细胞和巨噬细胞明显多于正常胰腺，并且肥大细胞的数量与淋巴结转移的存在直接相关。然而，浸润炎症细胞的数量与肿瘤周围实质中慢性胰腺炎（CP）样变化的存在之间没有关系。双重免疫染色显示胰腺肥大细胞和巨噬细胞均表达 VEGF-A、VEGF-C 和 bFGF。在许多情况下，这些因子也在肿瘤细胞中表达。表达VEGF-A的肿瘤细胞和表达bFGF的肿瘤和炎症细胞的数量与IMD显着相关。此外，IMD较高的肿瘤具有较高数量的浸润性肥大细胞和巨噬细胞。结论：非特异性免疫反应的单核炎症细胞被招募到胰腺癌组织中，与CP样变化的存在无关，可能影响癌细胞的转移能力，并可能有助于具有高血管生成活性的肿瘤的发展。
Background: Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness.Aims: To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance. Methods: Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor ( bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker.Results: There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages.Conclusions: Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.