Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression-related changes

Abstract

Purpose: Lung cancer is a biologically diverse disease and relevant models reflecting its diversity would facilitate the improvement of existing therapies. With a view to establishing such models, we developed and evaluated xenografts of a variety of human lung cancers.

Experimental design: Using nonobese diabetic/severe combined immunodeficiency mice, subrenal capsule xenografts were generated from primary lung cancer tissue, including moderately and poorly differentiated squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, large cell undifferentiated carcinoma, and carcinosarcoma. After 4 to 12 weeks, xenografts were harvested for serial transplantation and comparison with the original tissue via histologic, chromosomal, and cytogenetic analyses.

Results: Xenografts were successfully established. H&E staining showed that xenografts retained major histologic features of the original cancers. Immunohistochemistry and fluorescence in situ hybridization confirmed the human origin of the tumor cells and development in xenografts of murine supportive stroma. Four transplantable lines were developed from rapidly growing tumors (>5 generations), i.e., a small cell lung carcinoma, large cell undifferentiated carcinoma, pulmonary carcinosarcoma, and squamous cell carcinoma. Analyses including spectral karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization, revealed that the xenografts were genetically similar to the original tumors, showing chromosomal abnormalities consistent with karyotypic changes reported for lung cancer.

Conclusions: The subrenal capsule xenograft approach essentially provides a living tumor bank derived from patient material and a means for isolating and expanding specific cell populations. The transplantable tumor lines seem to provide good models for studying various aspects of tumor progression and a platform for developing novel therapeutic regimens, with the possibility of patient-tailored therapies.