Breast cancer is a significant health concern, as it is the most common cancer in women worldwide and the second leading cause of cancer-related deaths in the United States. The main challenge in treating breast cancer is identifying which cases of ductal carcinoma in situ (DCIS) are likely to progress to invasive ductal carcinoma (IDC). DCIS, a non-invasive form of breast cancer, makes up around 20% of new breast cancer diagnoses each year. Although more than half of DCIS cases do not develop into invasive cancer, the lack of reliable predictive diagnostic tools often leads to aggressive treatments, such as surgery and radiation, for many patients, causing unnecessary physical discomfort and anxiety.
To help oncologists make more informed treatment decisions, researchers at GW have developed an innovative, non-invasive diagnostic method to assess the risk of DCIS progressing to IDC. This tool evaluates biomechanical features of breast tumor cells, such as significant changes in cell volume and stiffness due to crowding, as well as the localization of specific ion channel proteins like TRPV4 on the cell surface, which act as biomarkers of invasiveness. Statistical results from independent histological evaluations of pathologies and TRPV4 distributions from 39 patient specimens showed significantly higher proportions of plasma membrane TRPV4 association in high-grade DCIS (75%) and IDC (73%), which was not observed in lower-risk cases.
Representative regions of interest (ROIs) of TRPV4-stained immunohistochemistry images in different pathology phenotypes. In high-grade (HG)-DCIS and invasive ductal cancer (IDC) regions, TRPV4 shows clear plasma membrane association compared to intermediate-grade (IMG)-DCIS, atypical ductal hyperplasia (ADH), benign pathologies, as well as lower-grade DCIS cells and normal breast tissue. Scale bar = 20 μm.
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Cell crowding induces TRPV4 inhibition and its relocation to plasma membranes, implicating pro-invasive cell volume reduction mechanotransduction pathway bioRxiv, Published July 06, 2024