Proteins in extracellular vesicles could lead to early diagnosis and treatment of breast cancer metastasis

One woman is diagnosed with breast cancer every fourteen seconds somewhere across the globe — based on data showing that an approximate 2.3 million women worldwide were newly diagnosed with breast cancer in 2020.

In Singapore, it is the most common cancer among women, and will likely affect one in thirteen women in their lifespan. Although advances in medicine today allow for treatments for early-stage and non-metastatic breast cancer, advanced stage and metastatic breast cancer is considered incurable with current treatment options, with very poor prognosis.

The early detection of breast cancer metastasis is therefore paramount in the treatment of the condition, and a team of researchers discovered a non-invasive biomarker that could aid with earlier diagnosis. Led by Assistant Professor Minh Le from the Institute for Digital Medicine (WisDM) and Department of Pharmacology at the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine), and Associate Professor Andrew Grimson from the Department of Molecular Biology and Genetics at Cornell University, the researchers found that particles which are secreted by tumour cells, extracellular vesicles (EVs), displayed a high level of protein integrins αv and β1, in patients with locally advanced and metastatic breast cancer.

Asst Prof Le said, “Metastasis is the chief concern for breast cancer patients. The study highlights the potential of integrins αv and β1 as a promising prognostic and therapeutic target for patients with metastatic breast cancer. Our research has opened several doors, and we hope that future work will help develop new ways to assess, monitor and suppress this hallmark of cancer.”

Published in the Journal of Extracellular Vesicles, the team used an ultra-sensitive protein identification tool to obtain a set of protein expression profiles from the EVs of different metastatic breast cancer cell lines. They discovered that, among many candidate proteins, integrins αv and β1 were consistently overexpressed in EVs of high metastatic background. In addition, the team collaborated with Associate Professor Victor Lee, Senior Consultant, Department of Pathology, National University Hospital, and found a high level of integrin αv in samples from patients with stage III or IV breast cancer.

A working model for integrin αvβ1 in the tumour microenvironment

Details are in the caption following the image

(1) Breast cancer cells secrete EVs to mediate their communication with other cell types, including fibroblasts, endothelial cells and immune cells, in the tumour microenvironment (TME). The TME cells in turn support tumour growth, angiogenesis and metastasis. (2) EVs from metastatic breast cancer cells are enriched in integrin αvβ1 complex that is sorted into EVs by Gal-3 in the cells. (3) Integrin αvβ1 attaches EVs to fibronectin in the extracellular matrix (ECM) that may help to attract more host cells into the TME

He said, “Through the study, we discovered the potential of integrin αv as a new non-invasive biomarker for the early diagnosis of breast cancer metastasis.”

Assoc Prof Grimson added, “The study has led to fundamental insights in the underlying mechanisms of breast cancer metastasis. In addition to its clinical relevance, the research contributes to recent advances in the EV field, in that there are functionally distinct subsets of EVs, which can now be more readily identified and studied to understand their functions and potential as therapeutic targets in the tumour environment.”

Source – National University Of Singapore, Yong Loo Lin School Of Medicine

Zhang DX, Dang XTT, Vu LT, Lim CMH, Yeo EYM, Lam BWS, Leong SM, Omar N, Putti TC, Yeh YC, Ma V, Luo JY, Cho WC, Chen G, Lee VKM, Grimson A, Le MTN. (2022) αvβ1 integrin is enriched in extracellular vesicles of metastatic breast cancer cells: A mechanism mediated by galectin-3. J Extracell Vesicles 11(8):e12234. [article]

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