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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Radiosensitivity of Breast Cancer Cells Is Dependent on the Organ Microenvironment
Genyan Guo1,2, Ryan T Morse3, Jie Wang1,2,4
1Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Background:
Distant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer "metastases" in liver and lung organ-specific tissues.
Methods:
Liver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells.
Results:
The response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death.
Conclusions:
The therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.
Insights
Breast cancer cells show different responses to radiation therapy depending on the organ microenvironment. Liver biomatrix scaffolds made breast cancer cells more sensitive to radiation than lung biomatrix scaffolds.
Area of Science:
- Oncology
- Biomaterials Science
- Radiotherapy Research
Background:
- Distant metastasis is a primary cause of breast cancer mortality, with lung and liver commonly affected.
- Current research explores local radiation therapy for metastatic sites, but organ-specific microenvironment effects are poorly understood.
- Biomatrix scaffolds (BMSs) were used to mimic native organ extracellular matrices for studying radiotherapy response in engineered breast cancer metastases.
Purpose of the Study:
- To investigate the impact of organ-specific microenvironments on breast cancer cell response to radiotherapy.
- To compare the radiosensitivity of breast cancer cells cultured in liver and lung biomatrix scaffolds.
- To analyze the role of Reactive Oxygen Species (ROS) in mediating radiotherapy effects within different microenvironments.
Main Methods:
- Preparation of liver and lung biomatrix scaffolds (BMSs) for tissue culture.
- Culturing human breast cancer cell lines on standard plates, Matrigel, liver BMSs, and lung BMSs.
- Conducting clonogenic assays to assess cell survival post-irradiation and Reactive Oxygen Species (ROS) detection assays.
Main Results:
- Breast cancer cell radiosensitivity varied based on the in vitro acellular microenvironment; liver BMSs increased radiosensitivity compared to lung BMSs.
- Higher ROS levels were observed in breast cancer cells cultured in lung and liver BMSs compared to standard or Matrigel plates, both before and after radiotherapy.
- Radiotherapy significantly increased ROS levels in both lung and liver BMSs, indicating a pro-death environment for cancer cells.
Conclusions:
- The organ-specific microenvironment significantly influences the therapeutic response of breast cancer metastases to radiotherapy.
- Understanding these microenvironmental interactions is crucial for identifying potential therapeutic targets and optimizing radiation delivery strategies.
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