Daniel L, Durbec P, Gautherot E, Rouvier E, Rougon G, Figarella-Branger D
Laboratoire de Biopathologie Nerveuse et Musculaire (JE2053). Institut de Biologie du Développement de Marseille, Marseille cedex 05, France.
Oncogene. 2001 Feb 22;20(8):997-1004. doi: 10.1038/sj.onc.1204176.
PSA is an oncodevelopmental antigen usually expressed in human tumors with high metastatic potential. Here we set up a metastatic model in nude mice by using TE671 cells, which strongly express PSA-NCAM. We observed the formation of lung metastases when TE671 cells were injected intravenously, intramuscularly, and intraperitoneally, but not subcutaneously. Intraperitoneal injections also induced peritoneal carcinosis, ascites, and liver metastases. To evaluate the putative role of PSA in the metastatic process we used a specific cleavage of PSA on NCAM by endoneuraminidase-N on intraperitoneal primary tumors. Mice with primary intramuscular tumors were taken as control. Repeated injections of endoneuraminidase-N led to a decrease in PSA expression in primary intraperitoneal nodules and ascites but not in intramuscular primary tumors. Endoneuraminidase-N also increased the delay in ascitic formation and decreased the number of lung or liver metastases in the case of intraperitoneal tumors but not in the case of intramuscular tumors. When metastases occurred in endoneuraminidase-N injected animals, they strongly expressed PSA-NCAM. Therefore, we established a relationship between PSA expression on the surface of primary tumor cells and the metastatic process.
前列腺特异性抗原(PSA)是一种肿瘤发育抗原,通常在具有高转移潜能的人类肿瘤中表达。在这里,我们使用强烈表达PSA-NCAM的TE671细胞在裸鼠中建立了转移模型。当通过静脉内、肌肉内和腹腔内注射TE671细胞时,我们观察到肺转移的形成,但皮下注射则未观察到。腹腔内注射还诱导了腹膜癌、腹水和肝转移。为了评估PSA在转移过程中的假定作用,我们使用神经氨酸酶-N对腹腔内原发性肿瘤上的NCAM上的PSA进行特异性切割。以原发性肌肉肿瘤小鼠作为对照。重复注射神经氨酸酶-N导致腹腔内原发性结节和腹水中PSA表达降低,但肌肉内原发性肿瘤中未降低。神经氨酸酶-N还增加了腹水形成的延迟,并减少了腹腔内肿瘤情况下肺或肝转移的数量,但肌肉内肿瘤情况下则没有。当在注射神经氨酸酶-N的动物中发生转移时,它们强烈表达PSA-NCAM。因此,我们建立了原发性肿瘤细胞表面的PSA表达与转移过程之间的关系。