Characterization of Lewis lung clonal variants in a model of syngeneic pulmonary murine metastases.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality world-wide. Since the majority of cancer deaths result from metastatic complications, understanding cellular alterations contributing to organ specific metastases is a continuing cancer research goal. Desirable models involve easy, efficient methodologies for development of pulmonary metastases utilizing genetically related syngeneic tumor cell lines varying in clonogenic frequency and growth rate for comparative studies. This work focused on development and characterization of primary and metastatic Lewis lung subclones (LLCC3, LLC1, LLCab) in a histocompatible C57B1/6 model. Surgical resection of primary tumors utilizing these cell lines resulted in reliable development of pulmonary metastases (> 90% of injected mice), while tail-vein injection proved sporadic (20% of injected mice). The preliminary analysis of selected cell-surface molecules indicates potential genetic differences that may underlie phenotypic variations. The combination of subcutaneous resection methodology and variant cell lines results in robust metastatic lung cancer for testing potential therapeutic interventions.