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Science Forum Index » Medicine - Cancer Forum » An In Vivo Mouse Model for Human Prostate Cancer...
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 Posted: Wed Jul 30, 2008 12:03 am |
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http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18392141
Neoplasia. 2008 April; 10(4): 371–379.
PMCID: PMC2288546
An In Vivo Mouse Model for Human Prostate Cancer Metastasis1,2,3
[Excerpts]
Aaron M Havens,*† Elisabeth A Pedersen,* Yusuke Shiozawa,* Chi Ying,‡
Younghun Jung,* Yanxi Sun,*§ Chris Neeley,‡ Jincheng Wang,* Rohit Mehra,‡
Evan T Keller,? Laurie K McCauley,*¶ Robert D Loberg,‡ Kenneth J Pienta,‡
and Russell S Taichman*
*Department of Periodontics and Oral Medicine, University of Michigan
School of Dentistry, Ann Arbor, MI 48109, USA
†Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA, 02115,
USA
‡Department of Internal Medicine, Division of Hematology/Oncology,
University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
§Department of Ophthalmology, Nanjing Tongren Hospital, Nanjing, Jiangsu
Province, China
?Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA
¶Department of Pathology, University of Michigan School of Medicine, Ann
Arbor, MI 48109, USA
Address all correspondence to: Russell S. Taichman, Department of
Periodontics and Oral Medicine, University of Michigan School of
Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109-1078. E-mail:
rtaich at (no spam) umich.edu
Received January 13, 2008; Revised January 29, 2008; Accepted January 30,
2008.
Top
Quote: Abstract
Introduction
Materials and Methods
Results
Discussion
Supplementary Material
References
Abstract
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, metastastic 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.
Top
Abstract
Quote: Introduction
Materials and Methods
Results
Discussion
Supplementary Material
References
Introduction
The metastatic spread of cancer cells is a dreaded complication of
malignant neoplasms. Metastasis is a multistep process in which malignant
cells must initially escape from the primary tumor, invade the surrounding
tissues, and enter the vascular circulation [1]. If they are able to
survive in the blood stream, they must successfully arrest at a secondary
target site, cross the vascular barrier, and migrate into the
extravascular connective tissues. Subsequently, tumor cells may
proliferate to form a clinically relevant metastatic colony.
Alternatively, they may remain dormant, potentially never proliferating
beyond a microscopic focus of cells. The molecular bases of metastasis
and, particularly, dormancy are poorly understood.
Having a primary tumor as a source of cancer cells is clearly a
prerequisite for establishing metastases. It is also clear that primary
tumors affect the host systemically, possibly priming distant tissues,
creating premetastatic niches that are conducive for tumor seeding [2–4].
This may influence both the seeding rate and/or growth of secondary
tumors. It may also precondition selective sites for the distinct
metastatic patterns as described by Paget [5] in the original
seed-and-soil hypothesis. Yet, to study each of these possibilities and,
in particular, early metastatic events, a model system must be in place,
which recapitulates what is observed clinically. Unfortunately, the number
of experimental systems of spontaneous metastasis using human prostate
cancer (PCa) cell lines is limited. Moreover, common systems used to
explore metastasis bypass many of the early steps in the process,
particularly when the tumor cells are placed directly into the
circulation.
To approach this problem, 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 PCa growth in severe combined immunodeficient (SCID) mice. For this
purpose, marked human PCa cell lines were implanted subcutaneously (s.c.)
or in the prostate (orthotopically) in SCID 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. These 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, metastastic 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. The model is highly adaptable
and amenable to experimental manipulation, and as such, the model will
clearly be useful to the scientific community in identifying the molecular
mechanisms of metastatic PCa disease.
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