Benkoël Liliane, Bernard Jean-Paul, Payan-Defais Marie-José, Crescence Lydie, Franceschi Cécile, Delmas Mireille, Ouaissi Mehdi, Sastre Bernard, Sahel José, Benoliel Anne-Marie, Bongrand Pierre, Silvy Françoise, Gauthier Laurent, Romagné François, Lombardo Dominique, Mas Eric
INSERM UMR 911-CRO2, Aix-Marseille Université, Faculté de Médecine-Timone, Marseille, France.
Mol Cancer Ther. 2009 Feb;8(2):282-91. doi: 10.1158/1535-7163.MCT-08-0471. Epub 2009 Feb 3.
We have shown that the 16D10 antigen located on the mucin-like COOH-terminal domain of the feto-acinar pancreatic protein (FAPP) is expressed at the surface of human pancreatic tumor cell lines such as SOJ-6 cell line. Furthermore, an in vivo study indicates that targeting this cell-membrane glycopeptide by the use of the monoclonal antibody (mAb) 16D10 inhibits the growth of SOJ-6 xenografts in nude mice. To validate the potential use of the mAb16D10 in immune therapy, this study examined the expression of 16D10 antigens at the surface of human pancreatic adenocarcinomas versus control tissues. We examined the reactivity of mAb16D10 and mAb8H8 with pancreatic ductal adenocarcinomas (PDAC) compared with controls by using immunohistochemistry and confocal laser scanning microscopy. mAb8H8 does react with control or nontumoral human pancreatic tissues. mAb16D10 has a strong and specific reactivity with PDAC and does not react with other cancers of epithelia or normal tissues tested. Notable, mAb16D10 mostly recognizes membrane of tumoral cells. Furthermore, mAb8H8 and mAb16D10 recognized a protein of 110 to 120 kDa in homogenates of nontumoral and tumoral human pancreatic tissues, respectively. This size correlates with that of FAPP or with that of the normal counterpart of FAPP, the so-called bile salt-dependent lipase. The results suggest that mAb16D10 presents a unique specificity against PDAC; consequently, it could be effective in immune therapy of this cancer. Furthermore, mAb16D10 and mAb8H8 pair might be useful for diagnosis purpose in discriminating tumoral from nontumoral human pancreatic tissues.
我们已经证明,位于胎儿胰腺腺泡蛋白(FAPP)粘蛋白样COOH末端结构域上的16D10抗原在人胰腺肿瘤细胞系如SOJ-6细胞系的表面表达。此外,一项体内研究表明,使用单克隆抗体(mAb)16D10靶向这种细胞膜糖肽可抑制裸鼠体内SOJ-6异种移植物的生长。为了验证mAb16D10在免疫治疗中的潜在用途,本研究检测了人胰腺腺癌与对照组织表面16D10抗原的表达。我们通过免疫组织化学和共聚焦激光扫描显微镜检查了mAb16D10和mAb8H8与胰腺导管腺癌(PDAC)相比对照的反应性。mAb8H8确实与对照或非肿瘤性人胰腺组织发生反应。mAb16D10与PDAC有强烈且特异性的反应,与所检测的其他上皮癌或正常组织无反应。值得注意的是,mAb16D10主要识别肿瘤细胞的膜。此外,mAb8H8和mAb16D10分别在非肿瘤性和肿瘤性人胰腺组织匀浆中识别出一种110至120 kDa的蛋白质。这个大小与FAPP或FAPP的正常对应物(即所谓的胆汁盐依赖性脂肪酶)的大小相关。结果表明,mAb16D10对PDAC具有独特的特异性;因此,它可能对这种癌症的免疫治疗有效。此外,mAb16D10和mAb8H8组合可能有助于在鉴别肿瘤性和非肿瘤性人胰腺组织中用于诊断目的。