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Human
Renal Cell Carcinoma Xenografts in SCID Mice: Tumorigenicity Correlates
with a Poor Clinical Prognosis |
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Eric Angevin,
Liubov Glukhova, Christine Pavon, Agnès Chassevent, Marie-Josée Terrier-Lacombe,
Anne-Françoise Goguel, Joëlle Bougaran, Patrice Ardouin, Bernard-Henri Court,
Jean-Louis Perrin, Guy Vallancien, Fréderic Triebel, Bernard Escudier |
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Unité
d'Immunothérapie (EA, CP, BE), Unité d'Immunologie Cellulaire (EA, FT),
Départements d'Anatomopathologie (M-JT-L) et de Chirurgie (B-HC, J-LP),
Laboratoire de Cytogénétique et Génétique Oncologiques UMR 1599 CNRS (LG,
A-FG), Service d'Expérimentation Animale (PA), Institut Gustave-Roussy,
Villejuif; Laboratoire de Radiobiologie (AC), Centre Paul Papin, Angers;
Départements d'Anatomopathologie (JB) et d'Urologie (GV), Institut Mutualiste
Montsouris, Paris, France |
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SUMMARY: To establish human
renal cell carcinoma (RCC) xenografts for preclinical studies, 55 renal
tumors (33 primary and 22 metastatic lesions) were transplanted subcutaneously
into severe combined immunodeficient mice. Twenty of 49 evaluable tumors
(40.8%) grew with a median latency period of 89 days (36 to 209 days) from
the day of engraftment. Tumor growth was stabilized after the fifth passage
with a median time between passages of 38 days (19 to 80 days). Tumorigenicity
was correlated with the metastatic phenotype of the tumor (54% success rate,
p = 0.007) and with reduced survival of patients. Despite a possible
evolution of histological features and tumor grading, established RCC xenografts
were comparable to parental tumors, as assessed by karyotype and DNA-ploidy
analyses. Molecular cytogenetic analysis also revealed specific genetic
alterations characterizing distinct RCC types that were constant in parental
and corresponding xenografts. In addition, this xenograft model has permitted
the selection of minor tumor subclones with a proliferative advantage and
minimal overexpressed chromosomal regions. We conclude that severe combined
immunodeficient mice are useful recipients for the establishment of long-term
RCC xenografts that can be used as valuable tools to evaluate the activity
of new therapeutic approaches and to study biological parameters determining
in vivo aggressiveness of human RCC. |
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