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Orthotopic Xenograft Mouse Model of Cervical Cancer for Studying the Role of MicroRNA-21 in Promoting Lymph Node Metastasis
  1. Wen-Fei Wei, MD*,
  2. Ling-Fei Han, PhD, MD,
  3. Dan Liu, PhD, MD,
  4. Lan-Fang Wu, MS§,
  5. Xiao-Jing Chen, MS*,
  6. Hong-Yan Yi, MS*,
  7. Xiang-Guang Wu, MS*,
  8. Mei Zhong, PhD, MD*,
  9. Yan-hong Yu, PhD, MD*,
  10. Li Liang, PhD, MD and
  11. Wei Wang, PhD, MD*,
  1. *Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong;
  2. Department of Minimally Invasive Gynecologic Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai;
  3. Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; and
  4. §Department of Obstetrics and Gynecology, Third Affiliated Hospital, and
  5. Department of Pathology, Nanfang Hospital, Southern Medical University; and
  6. Department of Obstetrics and Gynecology, Shenzhen Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China.
  1. Address correspondence and reprint requests to Wei Wang, MD, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Baiyun District, Guangzhou 510515, Guangdong, P.R. China. E-mail: smugowwang@126.com; or Li Liang, PhD, MD, Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China. E-mail: lli@fimmu.com.

Abstract

Abstract Cervical cancer is the most frequent cause of gynecologic cancer–associated death worldwide. Animal models that demonstrate metastatic patterns consistent with the clinical course of cervical cancer are urgently needed to conduct studies focused on understanding the mechanisms of the disease and identifying optimal treatments. To address this, we established an orthotopic xenograft model of cervical cancer in female NOD-SCID mice using SiHa and ME180 cell lines stably expressing green fluorescent protein to evaluate the role of microRNA-21 (miR-21) in spontaneous lymph node metastasis in vivo. In this case, SiHa and ME180 cells were transduced by lentivirus to stably express green fluorescent protein and miR-21. Overexpression of miR-21 promoted proliferation, migration, and invasion of SiHa and ME180 cells in vitro. Finally, an orthotopic xenograft model of human cervical cancer was successfully established in NOD-SCID mice. Using this model, we confirmed that overexpression of miR-21 resulted in an increase in the size of primary tumors and in the frequency of spontaneous lymph node metastasis at the time of excision. Therefore, the use of the orthotopic xenograft model should allow for the investigation of novel factors that affect metastasis of cervical cancer and presents an opportunity to evaluate potential therapeutic agents that may inhibit the spread of the disease.

  • Cervical cancer
  • Fluorescence stereomicroscope
  • Lymph node metastasis
  • MicroRNA-21
  • Orthotopic xenograft model

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Footnotes

  • W.-F.W., L.-F.H., and D.L. contributed equally to this work.

  • This work was supported by the National Science Foundation of China (nos. 81372781, 81072132, 81572546), the Natural Science Foundation of Guangdong Province and Shanghai Municipality (nos. S2013010014663, 15ZR1433300), and Science and Technology Program of Shenzhen (no. JCYJ20160429161218745).

  • The authors declare no conflicts of interest.

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