胰腺癌神经转移原位移植瘤动物模型的构建及其生物学特性研究

目的建立人类胰腺癌细胞系MIA PaCa—Ⅱ裸鼠胰腺原位移植瘤模型，观察神经侵袭情况，并研究其生物学特性。方法将MIA PaCa—Ⅱ细胞接种于裸鼠背部皮下和胰腺被膜下，建立皮下和原位移植瘤模型，分别于4、6、8周处死裸鼠行原位移植瘤病理学检查，HE和银染观察神经侵袭情况，对K—ras、C—erbB2、环氧合酶-2（COX-2）、前列腺干细胞抗原（PSCA）、p53、DPC4行SABC免疫组织化学染色。结果皮下移植瘤接种成瘤率为100％（10／10），呈局限性生长，无脏器和神经转移。原位移植4、6、8周时成瘤率均为100％（10／10），神经转移率分别为50％（5／10）、80％（8／10）和60％（6／10），并可见多个脏器转移。MIA PaCa—Ⅱ细胞、皮下及原位移植瘤细胞对K—ras、C—erbB2、COX-2、PSCA呈阳性表达，且高于裸鼠正常胰腺细胞，而p53、DPC4表达则低于正常胰腺组织细胞。结论成功建立神经侵袭原位移植瘤动物模型，研究嗜神经转移以6周为宜。K—ras、C—erbB2、COX-2、PSCA高表达与p53、DPC4低表达可能参与了胰腺癌的发生。

Establishment of a novel experimental neural invasion model with human pancreatic cancer and biological characters in vivo

Objective To establish a novel experimental neural invasion model with human pancreatic cancer cell line MIA PaCa-Ⅱand explore the biological characters. Methods The tumor mass which was formed by injecting human pancreatic cancer cell line MIA PaCa-Ⅱsubcutaneously was orthotopically transplanted into pancreas of nude mice. Morphological and biological features, metastasis and nerve invasion of the transplanted tumor were studied after 4, 6 and 8 weeks. Expression and distribution of K-ras, C-erbB2, COX-2, PSCA, p53 and DPC4 were detected in MIA PaCa-Ⅱ cell, with SABC immunohistochemistry. Results The successful rate of pancreatic cancer orthotopic implantation was all 100 % after 4, 6, and 8 weeks. The rate of nerve invasion was 50 %, 80 % and 60 % after 4, 6, and 8 weeks. Expression of K-ras, C-erbB2, COX-2 and PSCA were higher in pancreatic cancer cells than in normal pancreas cells. However, p53 and DPC4 expression were lower than normal. Conclusion Neural invasion model with human pancreatic cancer cell line MIA PaCa-Ⅱ orthotopic implantation tumor is successfully established in nude mice. The best time for exploring perinerval invasion is the sixth weeks. Every index studied may play important roles in the development of pancreatic cancer.