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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

The role of SWAP-70 in cancer metastasis and tumor immunity

Chang, Chao-Yuan 13 November 2023 (has links)
Cancer metastasis accounts for approximately 90% of all cancer-related deaths; however, the underlying mechanisms remain largely unknown. It has been known proteins that control F-actin dynamics are crucial for cancer metastasis. In this study, we revealed how an F-actin binding protein, Switch-associated protein 70 (SWAP-70), contributes to breast cancer metastasis. Moreover, immunotherapy is a promising approach to treat metastatic cancer cells by enhancing the function of the host immune system against cancer. Our lab has conducted extensive studies on how SWAP-70 regulates the function of several immune cell types, including dendritic cells (DCs), B cells, and mast cells. These cells have been reported to contribute to tumor immunity. Thus, we hypothesized that SWAP-70 plays a role in tumor immunity. To characterize the function of SWAP-70 in metastasis, we generated 4T1, mouse breast cancer, SWAP-70 knockout (KO) cells using Crispr/Cas9 technology. A syngeneic orthotopic model was used to recapitulate clinical disease progression, and the results showed that SWAP-70 led to significant metastasis to the lungs and bones in immunocompetent mice. Several functional assays have revealed that SWAP-70 promotes anchorage-independent growth, cell migration, invasion, and adhesion in 4T1 cells. Biophysical measurements showed that SWAP-70 contributes to cellular mechanics. To investigate how SWAP-70 in host cells affects tumor immunity, SWAP-70 deficient mice were injected with E0771 mouse breast cancer cells to study tumorigenicity. SWAP-70 deficient mice showed delayed primary tumor growth and less distant metastasis. Isolated SWAP-70−/− DCs were impaired in generating CD8 T cell responses pulsed with soluble OVA protein, but not with OVA peptide, suggesting that the antigen uptake, processing, and presentation process in SWAP-70−/− DCs may be diminished. Taken together, our findings describe the potential mechanisms by which the loss of SWAP-70 hinders cancer metastasis and provide several insights into how targeting SWAP-70 could be a potential therapeutic approach to target cancer.

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