Notch3 as a Novel Therapeutic Target in Metastatic Medullary Thyroid Cancer
Abstract
BackgroundMedullary thyroid cancer (MTC) portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in MTC liver metastasis will decrease tumor proliferation and growth. Method: TT cells... [ view full abstract ]
Background
Medullary thyroid cancer (MTC) portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in MTC liver metastasis will decrease tumor proliferation and growth.
Method:
TT cells were genetically modified to overexpress Notch3 in the presence of doxycycline, creating the TT-Notch3 cell line. Thirty-five mice were intrasplenically injected with either TT-Notch3 or control vector TT-TRE cells. Each cell line had three treatment groups: Control with 12 weeks of standard chow, Early Dox with doxycycline chow at day 0, and Late Dox with doxycycline chow at 8 weeks. Each animal underwent microCT-scanning at 8 and 12 weeks to evaluate for tumor formation, and tumor quantification was performed. Animals were sacrificed at 12 weeks, with harvested liver undergoing Ki-67, H&E, and Notch3 staining.
Results:
Comparing microCT-scans, we see the anti-proliferative effect of Notch3 induction (p=0.001). The TT-Notch3 treated group had a 37-fold decrease in tumor volume compared to the standard control. Comparing Late Dox TT-Notch3 group and control, Notch3 overexpression after tumor formation resulted in decreased Ki-67 index (p=0.038). TT-Notch3 tumors additionally showed increased areas of neutrophil infiltration and necrosis on H&E staining.
Conclusions:
Notch3 overexpression demonstrates an anti-proliferative effect on metastatic MTC liver tumors and is a potential therapeutic target in treatment.
Authors
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Irene Lou
(Universi)
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Scott Odorico
(University of Wisconsin - Madison)
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Xiao-min Yu
(University of Wisconsin - Madison)
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April Harrison
(University of Wisconsin - Madison)
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Renata Jaskula-Sztul
(University of Alabama - Birmingham)
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Herb Chen
(University of Alabama at Birmingham)
Topic Area
Endocrine Surgery
Session
QS-Br/Endo » Quick-Shot Presentations: Breast/Endocrine (15:00 - Thursday, 21st September, Bradley 400)