Tumor-Derived Loxl2 Is Highly Expressed In Myelofibrosis And Activating Mesenchymal Stem Cells Differentiate Into Cancer Associated Fibroblasts In Vitro

Abstract Background and objective: The disease progression of Myeloproliferative Neoplasms (MPN) is often accompanied by myelofibrosis, progressive myelofibrosis could be a high risk factor affecting the evolution of MPN into leukemia and bone marrow failure. Recently, Cancer associated fibroblasts (CAF) and lysyl-oxidase-like protein 2 (LOXL2) are found closely related to the process of myelofibrosis, but underlying molecular mechanism of how they mediate myelofibrosis is not yet fully understood.Mesenchymal Stem Cells (MSC) could differentiate into CAF in solid tumor. Here,we aim to investigate whether LOXL-2 could stimulate MSC into CAF and promote myelofibrosis in micro-environmental hypoxia. Methods and Results : Using a-SMA and FAP as marker for CAF. The mRNA and protein expression level of a-SMA ,LOXL2 and FAP in MPN with myelofibrosis were significantly higher than normal subjects ( P Conclusions : Here we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. BMMSCs from MPNs could obtain CAFs phenotype under MPNs bone marrow microenvironment and LOXL2 may be stimulating BMMSCs differentiate into CAFs by activated FAK/Src signaling pathway. Disclosures No relevant conflicts of interest to declare.