Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions
Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions
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DOI：
10.4161/cbt.4.7.1821
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发表时间：
2005-07-01
影响因子：
3.6
通讯作者：
Friess, H
中科院分区：
文献类型：
--
作者：
Kolb, A;Kleeff, J;Friess, H
胰腺导管腺癌（PDAC）是最具侵袭性的恶性肿瘤之一，总的5年生存率低于5%。肿瘤的侵袭性生长和早期转移是导致预后不良的两个重要原因。骨桥蛋白（OPN）是一种分泌性蛋白，在细胞粘附和迁移、炎症反应和凋亡等方面具有多种功能。在这项研究中，OPN在人类胰腺癌中的功能作用及其作为疾病标志物的潜在用途进行了分析。通过真实的时间定量PCR，与正常胰腺组织（n = 20）相比，胰腺癌（n = 23）和慢性胰腺炎（n = 22）样品中的OPN mRNA分别增加2.2倍和1.6倍。免疫组织化学分析显示，OPN染色在60%的原发性胰腺肿瘤和72%的淋巴结和肝转移。从胰腺癌患者（n = 70）、慢性胰腺炎患者（n = 12）和健康供体（n = 20）获得的血清样品的ELISA分析显示，肿瘤患者的OPN血清水平增加1.6倍，慢性胰腺炎患者增加1.9倍。重组人OPN显著增加胰腺癌细胞的侵袭力，而对细胞增殖没有任何影响。此外，通过特异性siRNA分子下调OPN可降低胰腺癌细胞的侵袭。总之，胰腺癌和慢性胰腺炎患者的OPN血清水平没有显著差异，从而限制了其作为预后或随访标志物的作用。然而，我们的研究结果确实表明，阻断OPN可能有助于抑制胰腺癌细胞的侵袭和转移。
Pancreatic ductal adenocarcinoma ( PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. Invasive tumor growth and early metastasis are two important reasons for this dismal prognosis. Osteopontin ( OPN) is a secretory protein with a variety of functions, for example in cell adhesion and migration, inflammatory reaction and apoptosis. In this study the functional role of OPN in human pancreatic cancer and its potential use as a disease marker were analyzed. By real time quantitative PCR, there was a 2.2- fold and 1.6- fold increase of OPN mRNA in pancreatic cancers (n = 23) and chronic pancreatitis samples (n = 22), respectively, compared to normal pancreatic tissues (n = 20). Immunohistochemical analysis demonstrated OPN staining in 60% of the primary pancreatic tumors and in 72% of the lymph node and liver metastases. ELISA analysis of serum samples obtained from pancreatic cancer patients (n = 70), chronic pancreatitis patients (n = 12), and healthy donors (n = 20) showed a 1.6-fold increase in OPN serum levels in patients with tumors and a 1.9-fold increase in patients with chronic pancreatitis. Recombinant human OPN significantly increased the invasiveness of pancreatic cancer cells, without having any impact on cell proliferation. In addition, downregulation of OPN by specific siRNA molecules decreased pancreatic cancer cell invasion. In conclusion, OPN serum levels in pancreatic cancer and chronic pancreatitis patients are not significantly different, thereby restricting its role as a prognostic or follow-up marker. Our results do suggest, however, that blockade of OPN might be useful as a therapeutic approach to inhibit invasion and metastasis of pancreatic cancer cells.