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

Date

Mar 15, 2023

Time

11:00 AM - 12:00 PM

Speaker

Frank Chao-Yuan Chang

Series

DIGS-ILS/IMPRS Doktorverteidigungen

Language

en

Main Topic

Medizin

Description

Frank Chao-Yuan Chang, Rolf Jessberger Group, will defend his PhD thesis
The role of SWAP-70 in cancer metastasis and tumor immunity
at the School of Medicine.

Everybody is welcome to attend!

Abstract

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.

Links

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Last modified: Mar 15, 2023, 7:36:22 AM