Abstract 1600: A xenograft model of spontaneous metastases in NOD SCID mice of human non-small cell lung cancer

Abstract

Abstract Introduction: Xenograft models of human non small cell lung cancer cell lines have been unreliable in studying distal organ metastases. Although the flank, as a primary xenograft site, is typically used for the convenience of measurement, rarely do even the most aggressive cell lines develop metastases. Methods: Using 15 anesthetized NOD.CB17-Prkdcscid/NcrCrl (NOD/SCID) mice, we xenografted 10,000 A549 cells into the liver under direct visualization and allowed the tumors to grow for 7 weeks. The mice were then euthanized, perfused with formalin, and grossly dissected. The liver, lung and spleen were processed, embedded in paraffin, sectioned and stained. A second group of 7 NOD/SCID mice were subsequently xenografted in the liver with A549, and a mouse each week was euthanized for 7 weeks and evaluated. Results: At 7 weeks, all 15 mice had gross primary tumor in the liver as well as grossly evident splenic (10/15) and mediastinal metastases (5/15). There were no gross pulmonary metastases observed (0/15). Histologic review, however, confirmed multiple microscopic foci of metastatic disease in all mice (15/15) throughout the lungs bilaterally, the mediastinal lymph nodes and spleen. Serially euthanized mice revealed histological evidence of a gradual spontaneous metastatic model system. Histologically evident primary tumor was apparent by week 1 with gross primary tumor development in the liver by week 2. Weeks 3 and 4 showed gross and histologic progression of primary tumor size with no apparent evidence of microscopic distal metastases. By week 5, the first histological findings of micrometastases appeared in the lungs which became wide spread in all the pulmonary parenchyma by week 7. Splenic and mediastinal lymph node involvement were observed histologically by week 6. Conclusions: Liver xenografting of A549 into NOD/SCID mice is a reliable way of developing widespread micrometastases to the lungs, mediastinal lymph nodes, and spleen. This model is clinically relevant since, unlike tail vein injection, it allows the study of the biology and treatment of a gradually developing primary lung tumor with subsequent metastatic spread. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1600. doi:10.1158/1538-7445.AM2011-1600