Oncotarget

Research Papers:

Preclinical, non-genetic models of lung adenocarcinoma: a comparative survey

Florian Janker, Walter Weder, Jae-Hwi Jang and Wolfgang Jungraithmayr _

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Oncotarget. 2018; 9:30527-30538. https://doi.org/10.18632/oncotarget.25668

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Abstract

Florian Janker1, Walter Weder1, Jae-Hwi Jang1,* and Wolfgang Jungraithmayr1,2,*

1Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland

2Department of Thoracic Surgery, Brandenburg Medical School, Neuruppin, Germany

*These authors have contributed equally to this work

Correspondence to:

Wolfgang Jungraithmayr, email: wolfgang.jungraithmayr@mhb-fontane.de

Keywords: lung cancer; mouse model; urethane; heterotopic; orthotopic

Received: November 14, 2017     Accepted: June 06, 2018     Published: July 17, 2018

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide. Animal models are key in analyzing cancer biology and therapy evaluation.

We here compared relevant non-genetic lung cancer models with regard to tumor induction period, incidence, morbidity and mortality rate and the immunological composition of primary tumors and the occurrence of tertiary lymphoid organs (TLO): (I) intraperitoneal Urethane injection (1g/kg), (II) Lewis lung carcinoma (LLC) cell line model (intravenous or subcutaneous), and (III) ex vivo three-dimensional (3D) primary cell culture model established from subcutaneously developed LLC-induced tumors.

The incidence of Urethane induced lung tumors was 100% in both, C57BL/6 and BALB/c strains without morbidity or mortality at twenty weeks after injection. The mean size of tumor nodules after Urethane injection was significantly larger in BALB/c mice vs. C57BL/6 (p<0.01). Three times of Urethane injection produced significantly more tumor nodules in both mouse strains compared to one injection (BALB/c: p<0.01; C57BL/6: p<0.05). TLOs were only found in the Urethane-induced model. Although the cell line models also showed 100% induction rate, morbidity was high due to skin ulceration on the inoculation site and the development of pleural effusions in the subcutaneous model and the intravenous model, respectively. Tendencies, but no significant differences (p>0.05) could be found in the count of CD4+, CD8+, F4/80+ and NKp46+ cells in a tumor nodule among investigated models.

All discussed models provided a high tumor incidence rate. TLOs were exclusively found in the Urethane-induced model. No significant difference could be found regarding immune cells across models.


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