Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Reagents
2.2. Establishment of Adipocyte-Specific ATX Knockout Mice as a Breast Cancer Model with IOA-289 Treatment
2.3. Establishment of Hybrid PyMT/Adipocyte ATX Knockout Mice and Monitoring Spontaneous Breast Tumor Development and Metastasis
2.4. ATX Activity Measurement
2.5. Effects of Feeding a High fat Diet on ATX Activity and tumor Growth
2.6. Bioinformatics Analysis
2.7. Multiplex Protein Measurement
2.8. Hydroxyproline Measurement
2.9. Quantitative PCR
2.10. Immunohistochemistry
2.11. Tumor Digestion and Cell Sorting
2.12. Statistical Analysis
3. Results
3.1. Breast Tumor Growth Was Suppressed by Inhibiting ATX with IOA-289 but Not by ATX Knockout in Adipocytes
3.2. Identification of Cells in E0771 and Human Breast Tumors That Can Synthesize ATX and the Functions of ATX in the Human Breast Tumor Microenvironment
3.3. IOA-289-Induced Changes on Plasma Cytokines/Chemokines in Blood Plasma and Tumors
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ATX | autotaxin |
IHC | immunocytochemistry |
LPA | Lysophosphatidate, lysophosphatidic acid |
LPC | Lysophosphatidylcholine |
KO | knockout |
MMP | matrix metalloproteinase |
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Tang, X.; Morris, A.J.; Deken, M.A.; Brindley, D.N. Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not. Cancers 2023, 15, 2937. https://doi.org/10.3390/cancers15112937
Tang X, Morris AJ, Deken MA, Brindley DN. Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not. Cancers. 2023; 15(11):2937. https://doi.org/10.3390/cancers15112937
Chicago/Turabian StyleTang, Xiaoyun, Andrew J. Morris, Marcel A. Deken, and David N. Brindley. 2023. "Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not" Cancers 15, no. 11: 2937. https://doi.org/10.3390/cancers15112937