Friess H, Guo X Z, Berberat P, Graber H U, Zimmermann A, Korc M, Büchler M W
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Int J Cancer. 1998 Aug 21;79(4):349-55. doi: 10.1002/(sici)1097-0215(19980821)79:4<349::aid-ijc7>3.0.co;2-v.
KAI1 belongs to a structurally distinct family of membrane glycoproteins, which function via cell-cell and cell-extracellular matrix interactions, thereby potentially influencing the ability of cancer cells to invade tissues and to metastasize into lymph nodes and distant organs. In the present study, we examined KAI1 expression in lymph node and liver metastases in comparison with primary pancreatic cancer to evaluate its influence on metastasis. KAI1 mRNA analysis was performed by Northern blot analysis and in situ hybridization. In addition, the respective protein was studied by immunostaining. Fourteen primary pancreatic cancer samples in which no lymph node metastases were present and 25 primary pancreatic cancer samples in which lymph node metastases were present at the time of tumor resection were included. In 20 of these cases, primary pancreatic cancer tissues and corresponding lymph node metastases from the same patient were studied. Furthermore, 11 liver metastases were available for KAI1 analysis. Increased steady-state levels of KAI1 mRNA were found in 33/39 (85%) primary pancreatic cancers in comparison with normal controls. Statistical analysis of KAI1 mRNA levels and clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher in non-metastasized tumors compared with tumors in which lymph node or distant metastases were present. In lymph node metastases KAI1 mRNA expression was lower than in the corresponding primary tumors: In 14 of 20 lymph node metastases no KAI1 mRNA expression and in 6 of 20 lymph node metastases only weak KAI1 mRNA levels were present in some cancer cells. Cancer cells of distant metastases were devoid of or exhibited low KAI1 mRNA levels compared with those of primary pancreatic cancers. A similar pattern was observed by immunostaining. These data support the hypothesis that KAI1 gene expression might influence the metastatic ability of pancreatic cancer cells in vivo. Reduction of KAI1 appears to promote cancer cell spread in lymph nodes and distant organs.
KAI1属于一个结构独特的膜糖蛋白家族，其通过细胞间和细胞与细胞外基质的相互作用发挥功能，从而可能影响癌细胞侵袭组织以及转移至淋巴结和远处器官的能力。在本研究中，我们检测了KAI1在淋巴结和肝转移灶中的表达，并与原发性胰腺癌进行比较，以评估其对转移的影响。通过Northern印迹分析和原位杂交进行KAI1 mRNA分析。此外，通过免疫染色研究相应的蛋白质。纳入了14例无淋巴结转移的原发性胰腺癌样本和25例在肿瘤切除时存在淋巴结转移的原发性胰腺癌样本。在其中20例病例中，研究了同一患者的原发性胰腺癌组织和相应的淋巴结转移灶。此外，有11个肝转移灶可用于KAI1分析。与正常对照相比，在33/39（85%）的原发性胰腺癌中发现KAI1 mRNA的稳态水平升高。对患者的KAI1 mRNA水平和临床参数进行统计分析发现，与存在淋巴结或远处转移的肿瘤相比，未转移肿瘤中的KAI1 mRNA水平显著更高。在淋巴结转移灶中，KAI1 mRNA表达低于相应的原发性肿瘤：在20个淋巴结转移灶中的14个中，无KAI1 mRNA表达，在另外20个淋巴结转移灶中的6个中，仅在一些癌细胞中存在较弱的KAI1 mRNA水平。与原发性胰腺癌相比，远处转移癌细胞中KAI1 mRNA水平缺失或较低。免疫染色观察到类似的模式。这些数据支持以下假设，即KAI1基因表达可能影响体内胰腺癌细胞的转移能力。KAI1的减少似乎促进癌细胞在淋巴结和远处器官中的扩散。
