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Experimental Models of Prostate Cancer
Bone Metastasis
- Establishment, characterization and imaging of
xenograft bone metastasis models -
PhD thesis presented by
Marta Garcia López
To obtain the degree of
PhD for the Universitat Autònoma de Barcelona (UAB)
PhD thesis done at the Research Unit in Biomedicine and Translational and Pediatrics
Oncology, at the Vall d’Hebron Research Institute, Vall d’Hebron Hospital,
under the supervision of Drs.
Jaume Reventós i Puigjaner, Andreas Doll and Juan Morote Robles
Doctoral study in Biochemistry, Molecular Biology and Biomedicine. Universitat Autònoma
de Barcelona, Faculty of Bioscience, Department of Biochemistry and Molecular Biology
Universitat Autònoma de Barcelona, 2013
Dr. Jaume Reventós Puigjaner Dr. Andreas Doll Dr. Juan Morote Robles
Marta Garcia López

No entiendes realmente algo a menos que seas capaz
de explicárselo a tu abuela.
Albert Einstein

Summary
In industrialized countries, prostate cancer (PCa) is the most common malignancy
in men, but mortality rates are much lower than those recorded in developing countries,
reflecting benefits from advances in early diagnosis and effective treatment. However,
the metastatic disease rather than the primary tumour is responsible for much of the
resulting morbidity and mortality. Skeletal metastases occur in more than 70% of cases
of late-stage of PCa and they confer a high level of morbidity, a 5-year survival rate of
25% and median survival of approximately 40 months. Though fractures and spinal cord
compression are potential complications, the most common symptom of bone
metastases is pain. Bone metastases from PCa lead to an accelerated bone turnover
state that features pathological activation of both osteoblasts and osteoclasts. Raised
activation of osteoclasts is directly correlated with an increased incidence of skeletal
complications, cancer progression and death. Further, once tumour metastasizes to
bone, the metastatic disease become incurable and current therapies are palliative and
mostly target either tumour cells or osteoclasts.
Thus, to better understand the biology of PCa bone metastasis and to investigate
new therapy options it is crucial to develop new animal models.
In this thesis, we have established new experimental models of PCa bone
metastasis by intraosseous (i.o.), intracardiac (i.c.) or intratibial (i.t.) inoculation of
human PCa cells in immunodeficient mice. Extensive bone metastasis were monitored
by in vivo bioluminescence imaging. Different strategies were performed to describe
new molecular targets involved in the mechanisms of PCa bone metastasis and to make
a suitable model for evaluating novel compounds as future therapeutic approaches.
To conclude, these models provide a reliable reproduction of the clinical situation
and allows characterization and design effective treatments by better understanding the
molecular mechanisms of PCa bone metastasis.