Mathematical modeling of tumor cell proliferation kinetics and label retention in a mouse model of lung cancer
Menée à l'aide d'un modèle murin de cancer du poumon induit par le gène Kras, cette étude présente un modèle mathématique et statistique rendant compte de l'existence d'une population cellulaire à faible taux de renouvellement dans les tumeurs
Slowly-cycling tumor cells that may be present in human tumors may evade cytotoxic therapies, which tend to be more efficient at destroying cells with faster growth rates. However, the proportion and growth rate of slowly-cycling tumor cells is often unknown in preclinical model systems used for drug discovery. Here we report a quantitative approach to quantitate slowly-cycling malignant cells in solid tumors, using a well-established mouse model of Kras-induced lung cancer (KrasG12D/+). Bromodeoxyuridine (BrdU) was administered to tumor-bearing mice and samples were collected at defined times during pulse and chase phases. Mathematical and statistical modeling of the label-retention data during the chase phase supported the existence of a slowly-cycling label-retaining population in this tumor model and permitted the estimation of its proportion and proliferation rate within a tumor. The doubling time of the slowly cycling population was estimated at ~5.7 weeks and this population represented ~31% of the total tumor cells in this model system. The mathematical modeling techniques implemented here may be useful in other tumor models where direct observation of cell cycle kinetics is difficult and may help evaluate tumor cell subpopulations with distinct cell-cycling rates.
Cancer Research , article en libre accès, 2013