Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models.
OBJECTIVE
Tumors grafted s.c. or under the mammary fat pad (MFP) rarely develop efficient metastasis. By applying bioluminescence imaging (BLI) technology, the MDA-MB-435-HAL-Luc subrenal capsule (SRC) model was compared with the MFP model for disease progression, metastatic potential, and response to therapy.


METHODS
The luciferase-expressing MDA-MB-435-HAL-Luc cell line was used in both MFP and SRC models. BLI technology allowed longitudinal assessment of disease progression and the therapeutic response to PD-0332991, Avastin, and docetaxel. Immunohistochemical analysis of Ki67 and CD31 staining in the primary tumors was compared in these models. Caliper measurement was used in the MFP model to validate the BLI quantification of primary tumors.


RESULTS
The primary tumors in MDA-MB-435-HAL-Luc MFP and SRC models displayed comparable growth rates and vascularity. However, tumor-bearing mice in the SRC model developed lung metastases much earlier (4 weeks) than in the MFP model (>7 weeks), and the metastatic progression contributed significantly to the survival time. In the MFP model, BLI and caliper measurements were comparable for quantifying palpable tumors, but BLI offered an advantage for detecting the primary tumors that fell below a palpable threshold and for visualizing metastases. In the SRC model, BLI allowed longitudinal assessment of the antitumor and antimetastatic effects of PD-0332991, Avastin, and docetaxel, and the results correlated with the survival benefits of these agents.


CONCLUSIONS
The MDA-MB-435-HAL-Luc SRC model and the MFP model displayed differences in disease progression. BLI is an innovative approach for developing animal models and creates opportunities for improving preclinical evaluations of anticancer agents.
Zhang
Cathy
C
Department of Cancer Biology, Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California, USA. cathy.zhang@pfizer.com
Yan
Zhengming
Z
Arango
Maria E
ME
Painter
Cory L
CL
Anderes
Kenna
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007668:Kidney; D008164:Luminescent Proteins; D008175:Lung Neoplasms / Q000556:secondary; D042361:Mammary Glands, Human; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010879:Piperazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008164:Luminescent Proteins; D010879:Piperazines; D011725:Pyridines; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; C500026:palbociclib