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An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line.
Lab Invest. 2005 Nov; 85(11):1392-404.LI

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.

Authors+Show Affiliations

Department of Cancer Endocrinology, BC Cancer Agency, Vancouver, British Columbia, Canada. ywang@bccrc.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16155594

Citation

Wang, Yuwei, et al. "An Orthotopic Metastatic Prostate Cancer Model in SCID Mice Via Grafting of a Transplantable Human Prostate Tumor Line." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 85, no. 11, 2005, pp. 1392-404.
Wang Y, Xue H, Cutz JC, et al. An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line. Lab Invest. 2005;85(11):1392-404.
Wang, Y., Xue, H., Cutz, J. C., Bayani, J., Mawji, N. R., Chen, W. G., Goetz, L. J., Hayward, S. W., Sadar, M. D., Gilks, C. B., Gout, P. W., Squire, J. A., Cunha, G. R., & Wang, Y. Z. (2005). An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line. Laboratory Investigation; a Journal of Technical Methods and Pathology, 85(11), 1392-404.
Wang Y, et al. An Orthotopic Metastatic Prostate Cancer Model in SCID Mice Via Grafting of a Transplantable Human Prostate Tumor Line. Lab Invest. 2005;85(11):1392-404. PubMed PMID: 16155594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line. AU - Wang,Yuwei, AU - Xue,Hui, AU - Cutz,Jean-Claude, AU - Bayani,Jane, AU - Mawji,Nasrin R, AU - Chen,Wilfred G, AU - Goetz,Lester J, AU - Hayward,Simon W, AU - Sadar,Marianne D, AU - Gilks,C Blake, AU - Gout,Peter W, AU - Squire,Jeremy A, AU - Cunha,Gerald R, AU - Wang,Yu-Zhuo, PY - 2005/9/13/pubmed PY - 2006/1/6/medline PY - 2005/9/13/entrez SP - 1392 EP - 404 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 85 IS - 11 N2 - 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. SN - 0023-6837 UR - https://www.unboundmedicine.com/medline/citation/16155594/An_orthotopic_metastatic_prostate_cancer_model_in_SCID_mice_via_grafting_of_a_transplantable_human_prostate_tumor_line_ L2 - https://doi.org/10.1038/labinvest.3700335 DB - PRIME DP - Unbound Medicine ER -