ECTS2016 Cancer and Bone Oral Communications Oral Communications (18 abstracts)
New models of breast and lung cancer bone metastases for preclinical efficacy testing
Mari I. Suominen 1 , Urs B. Hagemann 2 , Yvonne Konkol 1 , Jenni Bernoulli 1 , Katja M. Fagerlund 1 , Roger M. Bjerke 2 , Jenny Karlsson 2 , Jussi M. Halleen 1 & Alan Cuthbertson 2
1Pharmatest Services Ltd, Turku, Finland; 2Bayer AS, Oslo, Norway.
In advanced ER+ve breast cancer, the propensity of bone involvement is 85%. Similarly in advanced lung cancer, 30–40% of patients develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available. We present herein the development of four mouse models of breast and lung cancer suitable for screening of new therapies.
Breast cancer cell lines BT-474 and MFM-223 represent ER+, i.e. luminal B, and basal subtype with AR expression, respectively. NSCLC cell line H226 originates from squamous cell carcinoma and H322 from adenocarcinoma of the lung. Cells were inoculated in the tibia of immunodeficient female mice. Half of the BT-474 inoculated mice had a s.c. slow release 17-beta estradiol pellet. The formation of bone lesions was monitored by X-ray imaging. For H226 transfected with luciferase, tumor growth was also followed by bioluminescence imaging (BLI). Finally, tumor growth and type of bone lesion was confirmed by histology.
Bone lesions occurred in 100% and 90% of animals with or without hormonal supplementation, respectively, four weeks after inoculation of BT-474 cells. Bone lesions were detected earlier in mice with estradiol pellet and were of lytic type, whereas bone lesions in mice without hormonal supplementation were osteoblastic. For MFM-223, bone lesions were observed 4–6 weeks after inoculation in 60–70% of the animals. With both lung cancer cell lines, all mice developed bone lesions detectable already two weeks after inoculation. H226luc cells developed osteoblastic-mixed lesions and H322 cells induced lytic lesions. Very interestingly, H226luc cells also formed lung metastases in all animals, as evidenced by BLI.
New osteoblastic and osteolytic bone lesion models representing different subtypes of breast and lung cancer were successfully established.
Volume 5
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