The Role of Macrophages in Tumor Cell Recurrence Following Radiation Therapy
Abstract/Contents
- Abstract
- Radiotherapy is an effective treatment modality for more than fifty percent of all cancer patients. However, pre-clinical evidence suggests that radiotherapy may increase the risk for tumor recurrence. This process may be mediated through the recruitment of circulating tumor cells (CTCs) by radiation-induced expression of the cytokine granulocyte macrophage colony stimulating factor (GM-CSF). The pathway by which GM-CSF recruits these CTCs continues to be an area of study. GM-CSF is known to promote the proliferation and recruitment of monocytes to a given location and induce their differentiation into macrophages. Macrophages have a variety of interactions with cancer and may promote tumor development or facilitate tumor cell death depending on the context. The goal of this project is to elucidate the role macrophages may have in the recruitment of CTCs in response to irradiation. To test this hypothesis, transwell invasion assays were performed to investigate the migration of different cell lines after irradiation as a proxy for CTC infiltration of cancerous tissue. We found an increased recruitment of tumor cells following irradiation of either macrophages (Raw 264.7) or tumor cell lines (4T1). However, no significant relationship was found for the recruitment of macrophages following irradiation of either macrophages or tumor cell lines. This suggests that tumor cells were attracted in response to irradiation, which is in line with previous literature showing irradiation of normal tissue inducing a similar recruitment of CTCs. To investigate the systemic effects of macrophage content on tumor growth, we also studied a cohort of mice bearing a single orthotopic breast tumor that is irradiated and injected with macrophages. We found a tumor-suppressive effect in mice with intravenous injections of macrophages when compared to the subcutaneous (control) injection of macrophages. Finally, we perform a pilot study which demonstrates tail-vein injected macrophage localization after radiotherapy. Overall, this study demonstrates evidence that macrophages play a role in tumor recurrence induced by radiation and suggest potential therapeutics through manipulation of macrophage content.
Description
| Type of resource | text |
|---|---|
| Date created | June 17, 2018 |
Creators/Contributors
| Author | Wang, Jonathan Xin | |
|---|---|---|
| Primary advisor | Graves, Edward | |
| Advisor | Feldman, Marcus | |
| Degree granting institution | Stanford University, Department of Biology, 2018 |
Subjects
| Subject | macrophages |
|---|---|
| Subject | CTCs |
| Subject | Mestastasis |
| Subject | Radiation therapy |
| Subject | Cancer |
| Genre | Thesis |
Bibliographic information
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- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred Citation
- Wang, Jonathan X and Graves, Edward and Feldman, Marcus. (2018). The Role of Macrophages in Tumor Cell Recurrence Following Radiation Therapy. Stanford Digital Repository. Available at: https://purl.stanford.edu/gj125bg9380
Collection
Undergraduate Theses, Department of Biology, 2018-2019
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- Contact
- jonwang1@stanford.edu
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