Work

TGFβ enhances platelet–breast‐cancer‐cell interaction and promotes platelet aggregation

Year: 2025

Type: article

Abstract: Platelets (PLTs) have a significant impact on tumor development and progression, particularly in breast cancer, and contribute to cancer-associated thrombosis (CAT). Transforming growth factor beta (TGFβ), which is abundantly secreted by PLTs, is known to promote cancer aggressiveness. Nevertheless, the role of TGFβ in the PLT-cancer-cell interaction is largely unexplored. This study investigates how TGFβ stimulation of MCF7 breast cancer cells affects their capacity to interact with PLTs and induce PLT aggregation. MCF7, pre-treated with TGFβ and then exposed to PLTs, exhibited enhanced epithelial-mesenchymal transition (EMT) and a significantly increased ability to bind PLTs in suspension, as well as to stimulate PLT activation and aggregation. Gene expression and surface protein analyses revealed that TGFβ induced the upregulation of MCF7 adhesion molecules such as integrin-αv/CD51 and galectin-3. Intriguingly, these effects were abolished when cells were plated at high density, suggesting that TGFβ signaling may be influenced by cell junction regulation. Furthermore, we selected specific inhibitors of integrin-αv (cilengitide) and galectin-3 (GB1107) that did not interfere with PLT aggregation itself. Cilengitide, but not GB1107, effectively reduced the increased PLT-MCF7 interaction induced by TGFβ. Both inhibitors, however, significantly diminished PLT aggregation triggered by TGFβ-treated MCF7 cells. Complementary analyses of proteomic datasets from breast cancer tissues demonstrated a significant positive correlation between TGFβ1 and the platelet marker integrin alpha-IIb (ITGA2B; also known as CD41), particularly in luminal A subtypes and in cancers with lymph node involvement. These findings suggest that TGFβ stimulation enhances PLT-breast-cancer cell interactions and promotes PLT aggregation through the upregulation of specific adhesion proteins, thereby potentially contributing to CAT and metastatic progression.

Source: FEBS Journal

DOI: 10.1111/febs.70279