دورية أكاديمية
FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells.
العنوان: | FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells. |
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المؤلفون: | Javidi-Sharifi N; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., Martinez J; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., English I; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., Joshi SK; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., Scopim-Ribeiro R; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., Viola SK; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., Edwards DK 5th; Knight Cancer Institute, Oregon Health & Science University, Portland, United States., Agarwal A; Knight Cancer Institute, Oregon Health & Science University, Portland, United States.; Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, United States., Lopez C; Knight Cancer Institute, Oregon Health & Science University, Portland, United States.; Center for Spatial Systems Biomedicine, Oregon Health & Science University, Portland, United States., Jorgens D; Knight Cancer Institute, Oregon Health & Science University, Portland, United States.; Center for Spatial Systems Biomedicine, Oregon Health & Science University, Portland, United States., Tyner JW; Knight Cancer Institute, Oregon Health & Science University, Portland, United States.; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, United States., Druker BJ; Knight Cancer Institute, Oregon Health & Science University, Portland, United States.; Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, United States.; Howard Hughes Medical Institute, Chevy Chase, United States., Traer E; Knight Cancer Institute, Oregon Health & Science University, Portland, United States.; Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, United States. |
المصدر: | ELife [Elife] 2019 Feb 05; Vol. 8. Date of Electronic Publication: 2019 Feb 05. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
مواضيع طبية MeSH: | Signal Transduction*, Exosomes/*metabolism , Fibroblast Growth Factor 2/*metabolism , Leukemia, Myeloid, Acute/*pathology , Mesenchymal Stem Cells/*metabolism , Receptor, Fibroblast Growth Factor, Type 1/*metabolism, Animals ; Cell Survival ; Cells, Cultured ; Disease Models, Animal ; Humans ; Mice ; Mice, Knockout |
مستخلص: | Protective signaling from the leukemia microenvironment leads to leukemia cell persistence, development of resistance, and disease relapse. Here, we demonstrate that fibroblast growth factor 2 (FGF2) from bone marrow stromal cells is secreted in exosomes, which are subsequently endocytosed by leukemia cells, and protect leukemia cells from tyrosine kinase inhibitors (TKIs). Expression of FGF2 and its receptor, FGFR1, are both increased in a subset of stromal cell lines and primary AML stroma; and increased FGF2/FGFR1 signaling is associated with increased exosome secretion. FGFR inhibition (or gene silencing) interrupts stromal autocrine growth and significantly decreases secretion of FGF2-containing exosomes, resulting in less stromal protection of leukemia cells. Likewise, Fgf2 -/- mice transplanted with retroviral BCR-ABL leukemia survive significantly longer than their +/+ counterparts when treated with TKI. Thus, inhibition of FGFR can modulate stromal function, reduce exosome secretion, and may be a therapeutic option to overcome resistance to TKIs. Editorial Note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). Competing Interests: NJ, JM, IE, SJ, RS, DE, AA, CL, DJ, JT, ET No competing interests declared, BD Is currently principal investigator or co-investigator on Novartis clinical trials. His institution, OHSU, has contracts with these companies to pay for patient costs, nurse and data manager salaries, and institutional overhead. He does not derive salary, nor does his lab receive funds from these contracts. (© 2019, Javidi-Sharifi et al.) |
التعليقات: | Erratum in: Elife. 2019 Mar 29;8:. (PMID: 30924767) |
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معلومات مُعتمدة: | 5F30CA186477-03 United States NH NIH HHS; U54 CA224019 United States CA NCI NIH HHS; F30 CA186477 United States CA NCI NIH HHS; U01 CA217862 United States CA NCI NIH HHS; R01 CA229875 United States CA NCI NIH HHS; F30 CA239335 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: FGF2; FGFR1; bone marrow stroma; cancer biology; drug resistance; exosomes; human; human biology; medicine; microenvironment; mouse |
المشرفين على المادة: | 103107-01-3 (Fibroblast Growth Factor 2) EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) |
تواريخ الأحداث: | Date Created: 20190206 Date Completed: 20200326 Latest Revision: 20240411 |
رمز التحديث: | 20240411 |
مُعرف محوري في PubMed: | PMC6363389 |
DOI: | 10.7554/eLife.40033 |
PMID: | 30720426 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2050-084X |
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DOI: | 10.7554/eLife.40033 |