| First Author | Zhang Y | Year | 2022 |
| Journal | Cancers (Basel) | Volume | 14 |
| Issue | 8 | PubMed ID | 35454853 |
| Mgi Jnum | J:349031 | Mgi Id | MGI:7645969 |
| Doi | 10.3390/cancers14081947 | Citation | Zhang Y, et al. (2022) Platelet-Derived PDGFB Promotes Recruitment of Cancer-Associated Fibroblasts, Deposition of Extracellular Matrix and Tgfbeta Signaling in the Tumor Microenvironment. Cancers (Basel) 14(8) |
| abstractText | Platelets constitute a major reservoir of platelet-derived growth factor B (PDGFB) and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. To address the specific role of platelet-derived PDGFB in the tumor microenvironment, we have created a mouse model with conditional knockout of PDGFB in platelets (pl-PDGFB KO). Lack of PDGFB in platelets resulted in 10-fold lower PDGFB concentration in the tumor microenvironment, fewer cancer-associated fibroblasts and reduced deposition of the extracellular matrix (ECM) molecules fibronectin and collagen I in the orthotopic RIP1-Tag2 model for pancreatic neuroendocrine cancer. Myosin light chain phosphorylation, promoting cell contraction and, consequently, the mechano-induced release of active transforming growth factor (TGF) beta from extracellular compartments, was reduced in tumors from pl-PDGFB KO mice. In agreement, TGFbeta signaling, measured as phosphorylated Smad2, was significantly hampered in tumors from mice lacking PDGFB in their platelets, providing a plausible explanation for the reduced deposition of extracellular matrix. These findings indicate a major contribution of platelet-derived PDGFB to a malignant transformation of the tumor microenvironment and address for the first time the role of PDGFB released specifically from platelets in the remodeling of the ECM in tumors. |
