Intrapulmonary inoculation of multicellular spheroids to construct an orthotopic lung cancer xenograft model that mimics four clinical stages of non-small cell lung cancer

Yingbo Huang, Yifan Lu, Mallika Vadlamudi, Shen Zhao, Melanie Felmlee, Roshanak Rahimian, Xin Guo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Introduction: Lung cancer leads in mortality among all types of cancer in US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Mice models of lung cancer based on subcutaneous or orthotopic inoculation of cancer cell suspension do not adequately mimic the progression of lung cancer in clinic. Methods: A549-iRFP cells (human NSCLC adenocarcinoma) were cultured to form multicellular spheroids (MCS), which were then inoculated intrapulmonarily into male athymic nude mice. The xenograft cancer development was monitored by in vivo fluorescent imaging and validated by open-chest anatomy, ex vivo fluorescent imaging, and histological studies. Results: The newly developed orthotopic xenograft model of lung cancer simulated all four clinical stages of NSCLC progression over one month: Stage 1) localized tumor at the inoculation site, Stage 2) multiple tumor nodules or larger tumor nodule on the same side of the lung, Stage 3) cancer growth on heart surface, and Stage 4) metastatic cancer on both sides of the lung. The model yielded high rates of postoperative survival (100%) and parenchymal tumor establishment (88.9%). The roughness of the inoculated MCS associated negatively with the time needed to develop metastatic cancer (p = .0299). Discussion: This new orthotopic xenograft model of NSCLC would facilitate the development of medications to treat lung cancer.

Original languageEnglish (US)
Article number106885
JournalJournal of Pharmacological and Toxicological Methods
Volume104
DOIs
StatePublished - Jul 1 2020

Bibliographical note

Funding Information:
This work was partially supported by University of the Pacific Seed Grant. We thank Prof. William Chan for access to the infrared fluorescent imaging system and Prof. John Livesey for access to the microplate reader and for suggestion on the manuscript.

Publisher Copyright:
© 2020

Keywords

  • Animal model
  • Cancer progression
  • Inoculation
  • Intrapulmonary
  • Methods
  • Multicellular spheroid
  • Non-small cell lung cancer
  • Orthotopic

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