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Establishment of a cervical cancer model via inoculating SiHa Cells into humanized severe combined immunodeficient mice
Purpose of investigation: To establish a human papillomavirus (HPV) 16 positive cervical cancer model in the humanized severe combined immunodeficient (SCID) mouse. Methods: A HPVl6 positive cervical carcinoma cell line (SiHa) was transplanted subcutaneously into SCID mice (SiHa-SCID); human peripheral blood lymphocyte (Hu-PEL) was transplanted intraperitoneally (Hu-PEL-SCID), Hu-PEL was transplated intraperitoneally and SiHa subcutaneously (Hu-PBL-SiHa-SCID), and, PBS was transplanted subcutaneously (PES-SCID) as a control. The biological and immunological features were investigated. Results: The transplanted tumor grew slowly and no metastasis was found. The survival time of Hu-PEL-SiHa-SCID was significantly longer than that of SiHa-SCID. HPV16 DNA could be detected in all of the tumor tissues, but not in peripheral blood and organ tissues. Human serum IgG levels in Hu-PBL-SCID and Hu-PBL-SiHa-SCID were significantly elevated following immunoreconstructed time elongating, and significantly higher in Hu-PEL-SiHa-SCID than those in Hu-PEL-SCID. The numbers of human CD3\ CD4+ and CDs+ T cells were significantly increased in the peripheral blood and spleen of Hu-PEL-SiHa-SCID and Hu-PELSCID mice, and significantly higher in Hu-PEL-SiHa-SCID than those of Hu-PEL-SCID mice. The weight of the spleen was significantly increased in Hu-PEL-SiHa-SCID. Tumor infiltrating lymphocytes (TILs) and human CD4+ T cells were detected in HuPEL-SiHa-SCID but not in SiHa-SCID mice. The spleen cells of Hu-PEL-SiHa-SCID mice displayed significantly stronger cytotoxicity to target cells than those of SiHa-SCID mice. No graft-versus-host disease (GVHD) was found in either Hu-PEL or Hu-PEL-SiHa-SCID mice. Conclusion: A HPVl6 positive cervical carcinoma model has been successfully established in SCID mice. This model can perfectly simulate the biological features of spontaneous human cervical cancer, and present anti-tumor immune response after the human immune system is reconstructed.