{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang Y"],"funding":["Swedish Research Council, The Swedish Prostate Cancer Federation","Swedish Cancer Society","Swedish Research Council"],"pagination":["1947"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9024906"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(8)"],"pubmed_abstract":["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) β from extracellular compartments, was reduced in tumors from pl-PDGFB KO mice. In agreement, TGFβ 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."],"journal":["Cancers"],"pubmed_title":["Platelet-Derived PDGFB Promotes Recruitment of Cancer-Associated Fibroblasts, Deposition of Extracellular Matrix and Tgfβ Signaling in the Tumor Microenvironment."],"pmcid":["PMC9024906"],"funding_grant_id":["20 1283 PjF 01 H","2020-02258","2016-03036"],"pubmed_authors":["Herre M","Zhang Y","Cedervall J","Kamali-Moghaddam M","Hellman L","Qiao Q","Olsson AK","Hamidi A","Miao Z","Manouchehri Doulabi E"],"additional_accession":[]},"is_claimable":false,"name":"Platelet-Derived PDGFB Promotes Recruitment of Cancer-Associated Fibroblasts, Deposition of Extracellular Matrix and Tgfβ Signaling in the Tumor Microenvironment.","description":"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) β from extracellular compartments, was reduced in tumors from pl-PDGFB KO mice. In agreement, TGFβ 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-22T19:01:57.936Z","creation":"2025-04-06T02:40:01.312Z"},"accession":"S-EPMC9024906","cross_references":{"pubmed":["35454853"],"doi":["10.3390/cancers14081947"]}}