Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis.
OBJECTIVE
Human uveal melanoma develops in one of the most capillary-rich tissues of the body and has a pure hematogenous dissemination. Radiodiagnostic examinations, such as ultrasonic diagnostic resonance imaging and chest radiographs plus liver enzyme studies in blood, are methods used to detect liver and other distant metastases in patients. Nevertheless, the mortality rate is high, because of the frequent occurrence of metastases and the lack of systemic therapy. Therefore, the development of novel anticancer strategies is urgent, and more sensitive and less invasive methods of detecting and monitoring in vivo tumor growth and metastatic disease in cancer models are needed.


METHODS
A luciferase (Luc)-positive human uveal melanoma cell line (OCM-1 FRT/luc) was established. Tumor cells were inoculated into the anterior chamber of murine eyes for induction of orthotopic growth or into the left heart ventricle to mimic hematogenous micrometastatic spread. Development of metastases and tumor growth was monitored weekly by whole-body bioluminescent reporter imaging (BLI).


RESULTS
Injection of cancer cells into the anterior chamber of the eye of mice closely mimicked orthotopic tumor growth of uveal melanoma. Tumor progression could be quantitatively monitored 3 weeks after inoculation of 10(5) OCM-1 FRT/luc cells. Of the mice injected, 83% exhibited a detectable tumor within 5 weeks. Intracardiac injection of tumor cells resulted in metastatic growth, especially in bone. Mice had bone (maxillofacial region and femora) and visceral (lung and mediastinum) metastases after 4 to 6 weeks. OCM-1 FRT/luc cells may also have a propensity to colonize the eye after intracardiac inoculation.


CONCLUSIONS
BLI enables continuous quantitative monitoring in the same animal of growth kinetics for each tumor and its metastases. This model will accelerate the understanding of the pathogenesis and treatment of uveal melanoma and metastasis.
Notting
Irene C
IC
Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. i.c.notting@lumc.nl
Buijs
Jeroen T
JT
Que
Ivo
I
Mintardjo
Ratna E
RE
van der Horst
Geertje
G
Karperien
Marcel
M
Missotten
Guy S O A
GS
Jager
Martine J
MJ
Schalij-Delfos
Nicoline E
NE
Keunen
Jan E E
JE
van der Pluijm
Gabri
G
D000818:Animals; D000867:Anterior Chamber / Q000473:pathology; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006338:Heart Neoplasms / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049408:Luminescent Agents / Q000378:metabolism; D008163:Luminescent Measurements; D008545:Melanoma / Q000473:pathology* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology*
D049408:Luminescent Agents; D008156:Luciferases