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Article

Short-Term Environmental Conditioning Enhances Tumorigenic Potential of Triple-Negative Breast Cancer Cells

by
Samantha S. Eckley
1,†,
Johanna M. Buschhaus
2,3,
Brock A. Humphries
3,
Tanner H. Robison
2,3,
Kathryn E. Luker
2 and
Gary D. Luker
2,3,4,*
1
Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
2
Department of Biomedical Engineering, University of Michigan College of Engineering and Medical School, Ann Arbor, MI 48109, USA
3
Department of Radiology Center for Molecular Imaging, University of Michigan Medical School, Ann Arbor, MI 48109, USA
4
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
Current address: University of Iowa, Office of Animal Resources, Iowa City, IA, USA.
Tomography 2019, 5(4), 346-357; https://doi.org/10.18383/j.tom.2019.00019
Submission received: 12 September 2019 / Revised: 8 October 2019 / Accepted: 6 November 2019 / Published: 1 December 2019

Abstract

Tumor microenvironments expose cancer cells to heterogeneous, dynamic environments by shifting availability of nutrients, growth factors, and metabolites. Cells integrate various inputs to generate cellular memory that determines trajectories of subsequent phenotypes. Here we report that short-term exposure of triple-negative breast cancer cells to growth factors or targeted inhibitors regulates subsequent tumor initiation. Using breast cancer cells with different driver mutations, we conditioned cells lines with various stimuli for 4 hours before implanting these cells as tumor xenografts and quantifying tumor progression by means of bioluminescence imaging. In the orthotopic model, conditioning a low number of cancer cells with fetal bovine serum led to enhancement of tumor-initiating potential, tumor volume, and liver metastases. Epidermal growth factor and the mTORC1 inhibitor ridaforolimus produced similar but relatively reduced effects on tumorigenic potential. These data show that a short-term stimulus increases tumorigenic phenotypes based on cellular memory. Conditioning regimens failed to alter proliferation or adhesion of cancer cells in vitro or kinase signaling through Akt and ERK measured by multiphoton microscopy in vivo, suggesting that other mechanisms enhanced tumorigenesis. Given the dynamic nature of the tumor environment and time-varying concentrations of small-molecule drugs, this work highlights how variable conditions in tumor environments shape tumor formation, metastasis, and response to therapy.
Keywords: fluorescence; bioluminescence; signaling; breast cancer fluorescence; bioluminescence; signaling; breast cancer

Share and Cite

MDPI and ACS Style

Eckley, S.S.; Buschhaus, J.M.; Humphries, B.A.; Robison, T.H.; Luker, K.E.; Luker, G.D. Short-Term Environmental Conditioning Enhances Tumorigenic Potential of Triple-Negative Breast Cancer Cells. Tomography 2019, 5, 346-357. https://doi.org/10.18383/j.tom.2019.00019

AMA Style

Eckley SS, Buschhaus JM, Humphries BA, Robison TH, Luker KE, Luker GD. Short-Term Environmental Conditioning Enhances Tumorigenic Potential of Triple-Negative Breast Cancer Cells. Tomography. 2019; 5(4):346-357. https://doi.org/10.18383/j.tom.2019.00019

Chicago/Turabian Style

Eckley, Samantha S., Johanna M. Buschhaus, Brock A. Humphries, Tanner H. Robison, Kathryn E. Luker, and Gary D. Luker. 2019. "Short-Term Environmental Conditioning Enhances Tumorigenic Potential of Triple-Negative Breast Cancer Cells" Tomography 5, no. 4: 346-357. https://doi.org/10.18383/j.tom.2019.00019

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