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Fig. 6 | BMC Medicine

Fig. 6

From: ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis

Fig. 6

The LGI1 mimetic inhibits metastatic burden in vivo. a LGI1MIM displays no toxicity in mice at low-, mid- and high-dose concentrations. NOD/SCID mice were administered a daily regimen of LGI1MIM by IP injection at three doses: 1 μg/mouse/day (n = 2), 10 μg/mouse/day (n = 2) and 100 μg/mouse/day (n = 2). Mouse weights were noted daily as a measure of LGI1MIM tolerability. b Schematic of LGI1MIM in vivo study to examine early metastatic seeding events. c Mean tumour volume in baseline study (top) determines baseline LGI1MIM tumour inhibition and the early seeding study (bottom) determines LGI1MIM effect on initial metastatic events (LGI1MIM = red; vehicle = blue). Either 1 × 106 (baseline study) or 8 × 105 (early seeding study) luciferase tagged LY2 cells were implanted into the mammary fat pad of NOD/SCID mice. Mice were treated with either vehicle (n = 2 mice baseline study; n = 7 mice early seeding study) or LGI1MIM at (100 μg/mouse/per day) (n = 2 control study; n = 7 metastatic study) for 6 weeks. LGI1MIM induced a substantial decrease in local tumour volume in the baseline study (mean 450 mm3 versus 150 mm3, calliper measurement), whereas no alteration was detected in the early metastatic seeding model. d Cumulative metastatic burden in vehicle- and LGI1MIM-treated mice. LGI1MIM significantly reduces metastatic burden (as measured by BLU log2 p/s). Two tailed Mann–Whitney test* p = 0.0111. e The ex vivo luciferase activity from brain metastases in vehicle-treated (top) and LGI1MIM-treated (bottom) mice. f Brain metastatic burden, BLU log2 p/s, was significantly reduced in LGI1MIM treated mice (red; n = 7 mice) versus vehicle control (blue; n = 7 mice). Two-tailed Mann–Whitney test* p = 0.0373

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