Bioluminescent orthotopic mouse models of human localized non-small cell lung cancer: feasibility and identification of circulating tumour cells.
BACKGROUND
Preclinical models of non-small cell lung cancer (NSCLC) require better clinical relevance to study disease mechanisms and innovative therapeutics. We sought to compare and refine bioluminescent orthotopic mouse models of human localized NSCLC.


METHODS
Athymic nude mice underwent subcutaneous injection (group 1-SC, n = 15, control), percutaneous orthotopic injection (group 2-POI, n = 30), surgical orthotopic implantation of subcutaneously grown tumours (group 3-SOI, n = 25), or transpleural orthotopic injection (group 4-TOI, n = 30) of A549-luciferase cells. Bioluminescent in vivo imaging was then performed weekly. Circulating tumour cells (CTCs) were searched using Cellsearch® system in SC and TOI models.


RESULTS
Group 2-POI was associated with unexpected direct pleural spreading of the cellular solution in 53% of the cases, forbidding further evaluation of any localized lung tumour. Group 3-SOI was characterized by high perioperative mortality, initially localized lung tumours, and local evolution. Group 4-TOI was associated with low perioperative mortality, initially localized lung tumours, loco regional extension, and distant metastasis. CTCs were detected in 83% of nude mice bearing subcutaneous or orthotopic NSCLC tumours.


CONCLUSIONS
Transpleural orthotopic injection of A549-luc cells in nude mouse lung induces localized tumour, followed by lymphatic extension and specific mortality, and allowed the first time identification of CTCs in a NSCLC mice model.
INSERM U1030 & Université Paris XI, Institut Gustave Roussy, Villejuif, France.
Pierre
P
Mordant
Yohann
Y
Loriot
Benoit
B
Lahon
Yves
Y
Castier
Guy
G
Lesèche
Jean-Charles
JC
Soria
Marie-Catherine
MC
Vozenin
Charles
C
Decraene
Eric
E
Deutsch
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D016019:Survival Analysis