An in vivo mouse model for human prostate cancer metastasis.
We developed a sensitive real-time polymerase chain reaction (QPCR) assay that allows us to track early lodging/homing events in vivo. We used this technology to develop a metastasis assay of human prostate cancer (PCa) growth in severe combined immunodeficient mice. For this purpose, marked human PCa cell lines were implanted subcutaneously or in the prostate (orthotopically) of severe combined immunodeficient mice as models of primary tumors. Mice were then sacrificed at various time points, and distant tissues were investigated for the presence of metastatic cells. At 3 weeks, a number of tissues were recovered and evaluated by QPCR for the presence of metastatic cells. The data demonstrate that several PCa cell lines are able to spread from the primary lesion and take up residence in distant sites. If the primary tumors were resected at 3 weeks, in several cases, metastatic lesions were identified over the course of 9 months. We propose that this new model may be particularly useful in exploring the molecular events in early metastasis, identifying the metastatic niche, and studying issues pertaining to dormancy.
Havens
Aaron M
AM
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
Pedersen
Elisabeth A
EA
Shiozawa
Yusuke
Y
Ying
Chi
C
Jung
Younghun
Y
Sun
Yanxi
Y
Neeley
Chris
C
Wang
Jincheng
J
Mehra
Rohit
R
Keller
Evan T
ET
McCauley
Laurie K
LK
Loberg
Robert D
RD
Pienta
Kenneth J
KJ
Taichman
Russell S
RS
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D004247:DNA