(W1083) SINGLE-CELL ANALYSIS REVEAL KEY PLAYERS IN TRANSFORMATIONS OF MESENCHYMAL STROMAL CELLS INTO CANCER-ASSOCIATED FIBROBLASTS AND METASTATIC-ASSOCIATED FIBROBLASTS IN THE BREAST CANCER
Director of Center of Excellence for Stem Cells and Regenerative Medicine Zewail City of Science and Technology October City, Al Jizah, Egypt
Abstract: Breast cancer is a leading cause of mortality in adult women, particularly when it metastasises. Cancer-associated fibroblast (CAF) in the tumor microenvironment (TME) significantly influences cancer spread and metastasis. CAF originate from fibroblasts and mesenchymal stromal cells (MSCs) within the TME and transform into metastatic-associated fibroblasts (MAFs). Research on CAFs often focuses on MSC behavior at the primary tumor sites post-stimulus, and few studies evaluate their fate and roles at the metastatic sites. By utilizing single-cell RNA sequencing (SC-RNA seq.) data of human breast cancer, we aim to clarify the pathways underlying the conversion of MSCs to CAFs and CAFs into MAFs. Data from primary breast cancer and secondary lymph node metastatic patients were retrieved and analysed from the GEO dataset. Clustering and annotation were performed to identify MSCs, CAFs, and MAFs in both primary and secondary tumor sites. Our data show that inflammatory CAFs (iCAFs) and matrix CAFs (mCAFs) were the predominant subtypes at the metastatic site. Trajectory analysis pinpointed perivascular MSCs (pMSCs) as the origin of both iCAFs and myofibroblastic CAFs (myoCAFs). Following cell-cell interaction analysis, the receptor-antigen interactions within the TME were anticipated. Upon performing a pseudo-bulk differential expression analysis, two metastatic biomarkers (NPY1R and CCDC102B) were shown to be exclusively expressed by inflammatory MAFs (iMAFs), implying potential targets for inhibiting breast cancer metastasis. Our data identify novel targets that may impede the conversion of MSCs into CAFs and CAFs into MAFs, which potentially impacts breast cancer diagnosis, prognosis, and treatment strategies.
Funding Source: Grant #46721 from the Egyptian Science and Technology Development Fund, Cairo, Egypt
