Peritoneal Metastases in a Patient-derived Orthotopic Xenograft (PDOX) Model of Colon Cancer Imaged Non-invasively via Red Fluorescent Protein Labeled Stromal Cells

Jun Ho Park, Ming Zhao, Hiromichi Oshiro, Kentaro Miyake, Takashi Higuchi, Jose Reynoso, Sahar Razmjooei, Michael Bouvet, Bryan Clary, Zhiying Zhang, Norihiko Sugisawa, Jun Yamamoto, Shree Ram Singh, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background/Aim: Patient-derived orthotopic xenograft (PDOX) models have patient-like clinical features and may be imaged, in case of some cancers, by passaging of the tumors through transgenic nude mice expressing red-fluorescent protein (RFP) where they stably acquire RFP expressing stroma. The aim of the present study was to quantify red fluorescent area and intensity in colon-cancer peritoneal metastases in PDOX models in non-transgenic nude mice after passage in RFP transgenic nude mice by non-invasive external fluorescence imaging. Materials and Methods: Tumor fragments originating from a colon cancer patient with peritoneal metastases were implanted in transgenic RFP nude mice. Resultant tumors were harvested, and fragments were implanted in the same strain a second time. Passaged tumors stably acquired RFP-expressing stroma from their transgenic hosts. The tumor with RFP-expressing stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. At eight weeks post-implantation, non-invasive external RFP images were obtained. RFP area and intensity were measured and correlated with tumor weight and volume. Results: Metastatic patient colon cancer can be stably and brightly labeled by passage in transgenic RFP-expressing nude mice such that tumor growth could be non-invasively imaged. Tumor growing could be non-invasively imaged when passaged to non-transgenic nude mice. A strong correlation between fluorescence intensity and area values with tumor weight and volume were established by external fluorescence imaging. Conclusion: This new tumor model of metastatic colon cancer can be used to evaluate novel therapeutics in real time for this recalcitrant disease.

Original languageEnglish
Pages (from-to)3463-3467
Number of pages5
JournalAnticancer research
Volume39
Issue number7
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Colon cancer
  • Noninvasive imaging
  • Patient-derived orthotopic xenograft
  • Peritoneal metastases
  • Red-fluorescent protein
  • Stromal cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Peritoneal Metastases in a Patient-derived Orthotopic Xenograft (PDOX) Model of Colon Cancer Imaged Non-invasively via Red Fluorescent Protein Labeled Stromal Cells'. Together they form a unique fingerprint.

Cite this