人免疫重建荷人HPV16阳性宫颈癌SCID鼠模型的建立及其生物学特征研究

Development of HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and its biological features.

目的 :建立人免疫重建荷人HPV16阳性宫颈癌 -严重联合免疫缺陷小鼠模型并研究其生物学特征。方法 :向严重联合免疫缺陷 (SCID)鼠腹腔注射人外周血淋巴细胞 (PBL)后 2 4h ,皮下接种HPV16阳性的人宫颈癌细胞株SiHa细胞建立人免疫重建荷人HPV16阳性宫颈癌SCID鼠模型 ,观察荷瘤鼠成瘤、一般特征和移植瘤生长、转移情况及组织学特征 ,检测外周血、肿瘤组织和肺脾等其它组织中HPV16DNA、血清中人IgG含量和移植物抗宿主情况。结果 :SCID小鼠成瘤率为 10 0 % ,移植瘤生长以局部浸润为主 ,未见转移瘤。免疫重建荷瘤组生存期 (136 .2± 6 .3d)显著长于未重建荷瘤组 (97.8± 3.7d) ;组织学检查示移植前后肿瘤细胞形态相似 ;所有肿瘤组织中HPV16DNA呈阳性 ,而外周血和肺脾等其它组织均为阴性。未发现移植物抗宿主情况。结论

Objective:To develop a HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and investigate its biological fetures.Methods:Thirty-two CB17 SCID mice were randomly divided into 4 groups:group A subcutaneously injected with phosphate-buffered saline,group B intraperitoneally injected with human peripheral blood lymphocyte(PBL) for immune reconstruction,group C subcutaneously injected with human cervical carcinoma cell line SiHa,and group D intraperitoneally injected with PBL and subcutaneously injected with SiHa cell.The rate of tumor transplantation,generic characteristic,tumor growth,metastasis and histological features, HPV16 DNA from peripheral blood,tumor tissue,liver,spleen,lung,kidney,caul,uterus and adnexa,human IgG in mouse serum and status of graftversus host disease(GVHD) were detected.Results:The successful rate of tumor transplantation was 100%.The transplantation tumor grew mostly by local invasion. Metastasis was not found.The survival days of group D(136.2±6.3days) was markedly longer than group C(97.8±3.7days). Human IgG was detected in humanized groups(B and D).The level of human IgG was significantly higher in group D than in group B(P<0.05).The histological appearance of tumor before or after transplanted was very similar.The positive rate of HPV16 DNA in tumor tissue was 100% while 0% in peripheral blood,liver,spleen,lung,kidney,caul,uterus and adnexa.No GVHD was found in all groups.Conclusion:A HPV16 positive cervical cancer model has been successfully established in hu-PBL-SCID mouse which simulates preferably the biological behavior of human spontaneous cervical carcinoma.