Purpose: Human xenografts in athymic mice are frequently used as preclinical models of cancer to investigate the targeting of drugs. In order to distinguish specific from nonspecific targeting of the xenograft, the mice can be implanted with different malignant cell lines. We studied in xenograft success and growth rates after implantation of human lymphoma and breast cancer cells to begin an assessment of the validity of this approach for distinguishing specific from nonspecific targeting. Investigations were undertaken to determine the effect of two different cell-line xenografts, and prior radiation needed for one of the xenografts, on implantation success and growth rates.
Experimental Design: Female athymic mice were given 4 Gy of external beam radiation 4 days prior to subcutaneous (s.c.) abdominal implantation of 6 ×106 Raji human lymphoma cells. One week later, 3 × 106 hamster blood transfusion (HBT) 3477 human breast cancer cells were implanted s.c. in a contralateral abdominal site. Xenografts were evaluated frequently thereafter. Xenograft success and growth rates were compared to those observed in "historical" control groups, wherein only a single xenograft of each type was implanted.
Results: Raji xenografts developed from 73.7% of the implantations, and 100% of the HBT 3477 xenografts were successful in the experimental group. The "historical" Raji xenograft success rate was 74.1%(±9.3%), and the "historical" HBT 3477 xenografts success rate was 99.0% (±1.1%). HBT 3477 xenografts did not affect the growth rate of the Raji xenografts, and the mean doubling time for the experimental Raji xenografts was 6.3 days (±4.5 days), compared to the "historical" control group mean of 5.1 days (±3.9 days; p = 0.2). Similarly, the growth rates for the HBT 3477 xenografts were not affected by the Raji xenografts and the preradiation needed for this model. Mean doubling time for HBT 3477 xenografts in the presence of Raji xenografts was 9.2 days (±17.6 days), compared to a doubling time of 1.4 days (±15.2 days; p = 0.55 and 0.94 studies 1 and 2, respectively). Mean HBT 3477 xenograft doubling time for the "historical" control group was 4.4 days (±6.0 days).
Conclusions: Implantation of Raji xenografts and HBT 3477 breast cancer xenografts in the same mouse did not affect xenograft success or growth rates, even when whole-body radiation of 4 Gy was used to promote Raji xenografts. These observations are not intended to imply an absence of differences in other biological parameters in this sytem or to encourage extrapolation of the conclusions indiscriminately to other preclinical models. Contrarily, our aim was to encourage other investigators to further validate these frequently used approaches.
