1. ¹Department of Cancer Endocrinology, BC Cancer Agency, Vancouver, British Columbia, Canada
2. ²Department of Anatomical Pathology, St Joseph's Hospital—Hamilton Health Sciences, Hamilton, Ontario, Canada
3. ³Department of Laboratory Medicine and Pathobiology, Ontario Cancer Institute, Toronto, Ontario, Canada
4. ⁴Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada
5. ⁵Urology Research Unit, Carlton Centre, San Fernando, Trinidad
6. ⁶Department of Urology, Gulf View Medical, La Romaine, Trinidad
7. ⁷Departments of Urologic Surgery and Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA
8. ⁸Department of Pathology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
9. ⁹Departments of Anatomy and Urology, University of California San Francisco, San Francisco, CA, USA

Correspondence: Dr Y-Z Wang, PhD, Department of Cancer Endocrinology, BC Cancer Agency—Research Centre, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3. E-mail: ywang@bccrc.ca

Received 3 March 2005; Revised 8 July 2005; Accepted 11 July 2005; Published online 12 September 2005.

Abstract

Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone.