Establishment of a patient-derived orthotopic xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern

Yukihiko Hiroshima, Yong Zhang, Nan Zhang, Ali Maawy, Sumiyuki Mii, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuuya Yano, Takashi Murakami, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Takuya Murata, Itaru Endo, Robert M. Hoffman

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Abstract

Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patientderived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient's cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient's cervical tumors resulted in primary growth but not metastasis.

Original languageEnglish
Article numbere0117417
JournalPLoS One
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 17 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hiroshima, Y., Zhang, Y., Zhang, N., Maawy, A., Mii, S., Yamamoto, M., Uehara, F., Miwa, S., Yano, S., Murakami, T., Momiyama, M., Chishima, T., Tanaka, K., Ichikawa, Y., Bouvet, M., Murata, T., Endo, I., & Hoffman, R. M. (2015). Establishment of a patient-derived orthotopic xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern. PLoS One, 10(2), [e0117417]. https://doi.org/10.1371/journal.pone.0117417