Short-Term Environmental Conditioning Enhances Tumorigenic Potential of Triple-Negative Breast Cancer Cells
| Autor: | Gary D. Luker, Tanner H. Robison, Johanna M. Buschhaus, Kathryn E. Luker, Brock Humphries, Samantha S. Eckley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Carcinogenesis
Cell Count Triple Negative Breast Neoplasms Tumor initiation mTORC1 Mechanistic Target of Rapamycin Complex 1 medicine.disease_cause Metastasis 03 medical and health sciences 0302 clinical medicine breast cancer Cell Line Tumor medicine Cell Adhesion Tumor Microenvironment Animals Humans Radiology Nuclear Medicine and imaging fluorescence bioluminescence signaling Neoplasm Metastasis Extracellular Signal-Regulated MAP Kinases Triple-negative breast cancer Research Articles 030304 developmental biology Cell Proliferation Sirolimus 0303 health sciences Tumor microenvironment Epidermal Growth Factor Chemistry Serum Albumin Bovine medicine.disease Disease Models Animal Tumor progression 030220 oncology & carcinogenesis Cancer cell Luminescent Measurements Cancer research Disease Progression Female Proto-Oncogene Proteins c-akt |
| Zdroj: | Tomography Volume 5 Issue 4 Pages 346-357 Tomography; Volume 5; Issue 4; Pages: 346-357 |
| ISSN: | 2379-1381 |
| DOI: | 10.18383/j.tom.2019.00019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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