Millions of people are diagnosed with breast cancer each year, and early detection of breast cancer metastatic risks is critical for effective treatment. Integrins bound to extracellular vesicles (EVs) have been shown play an important role in cancer metastasis and previous studies have found that specific integrins could serve as biomarkers for colorectal cancer, ovarian cancer and more. Now, researchers from the National University of Singapore Yong Loo Lin School of Medicine have identified integrins in the EVs of breast cancer cells that could aid in early diagnosis of metastasis.
The researchers performed comparative mass spectrometry in order to characterize EVs from both human and mouse breast cancer cell lines with different metastatic potentials. They also developed a two-step purification method that combined flotation ultracentrifugation with fast protein size-exclusion liquid chromatography (FPLC-SEC) in order to yield highly pure and intact EVs for the study. To further validate the levels of specific integrins on the EV surfaces, the researchers developed a magnetic bead-based flow cytometry assay, and also performed immunoprecipitation mass spectrometry to investigate the export mechanism of the target integrins into EVs.
The analysis showed that the integrins αv and β1 were consistently overexpressed in EVs of high metastatic background. The researchers worked with colleagues at Singapore National University Hospital and Guangxi Medical University to further understand the clinical prognostic value of these biomarkers in patient samples. High levels of integrin αv were found in samples from patients with stage III or stage IV breast cancer compared to those in earlier stages of the disease. Integrin αv was thus identified as a new non-invasive biomarker for early diagnosis of breast cancer metastasis, as the protein can be detected through blood testing, the authors wrote. This study was published in the Journal of Extracellular Vesicles.
“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,” said co-corresponding author Minh Le. “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.”
Co-corresponding author Andrew Grimson, of the Department of Molecular Biology and Genetics at Cornell University, added that the study also contributes to advances in the EV field, furthering understanding of their functions and their potential as therapeutic targets for cancer metastasis.