This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cutz, J.-C. Articles by Wang, Y.-Z. Search for Related Content PubMed PubMed Citation Articles by Cutz, J.-C. Articles by Wang, Y.-Z.

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

Authors' Affiliations: Departments of ¹ Cancer Endocrinology and ² Cancer Imaging, BC Cancer Agency, Departments of ³ Pathology and ⁴ Surgery, Vancouver General Hospital, Vancouver, British Columbia, ⁵ Department of Applied Molecular Oncology, Ontario Cancer Institute, University Health Network, and ⁶ Departments of Laboratory Medicine and Pathobiology, and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Requests for reprints: Yu-Zhuo Wang, Department of Cancer Endocrinology, BC Cancer Agency, Research Centre, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3. Phone: 604-675-8013; Fax: 604-675-8183; E-mail: ywang{at}bccrc.ca.

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.

This article has been cited by other articles:

				D. Lin, A. Watahiki, J. Bayani, F. Zhang, L. Liu, V. Ling, M. D. Sadar, J. English, L. Fazli, A. So, et al. ASAP1, a Gene at 8q24, Is Associated with Prostate Cancer Metastasis Cancer Res., June 1, 2008; 68(11): 4352 - 4359. [Abstract] [Full Text] [PDF]