کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151421 | 1089991 | 2012 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of Basophils as a Major Source of Hepatocyte Growth Factor in Chronic Myeloid Leukemia: A Novel Mechanism of BCR-ABL1-Independent Disease Progression
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کلمات کلیدی
mAbIL-3LUFHGFHUVECCMLFCSMNCHDCc-Met - c-metMonoclonal antibody - آنتی بادی مونوکلونالrecombinant human - انسان نوترکیبInterleukin 3 - اینترلوکین 3Peripheral blood - خون محیطیfetal calf serum - سرم گوساله جنینmononuclear cell - سلول تک هسته ایHepatocyte growth factor - عامل رشد هپاتوسیتBlast phase - فاز انفجارAccelerated Phase - فاز سریعchronic phase - فاز مزمنVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)Lung fibroblast - فیبروبلاست ریهChronic myeloid leukemia - لوسمی میلوئید مزمنbone marrow - مغز استخوانHistidine Decarboxylase - هیستیدین دکربوکسیلازpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chronic myeloid leukemia (CML) is a hematopoietic neoplasm characterized by the Philadelphia chromosome and the related BCR-ABL1 oncoprotein. Acceleration of CML is usually accompanied by basophilia. Several proangiogenic molecules have been implicated in disease acceleration, including the hepatocyte growth factor (HGF). However, little is known so far about the cellular distribution and function of HGF in CML. We here report that HGF is expressed abundantly in purified CML basophils and in the basophil-committed CML line KU812, whereas all other cell types examined expressed only trace amounts of HGF or no HGF. Interleukin 3, a major regulator of human basophils, was found to promote HGF expression in CML basophils. By contrast, BCR-ABL1 failed to induce HGF synthesis in CML cells, and imatinib failed to inhibit expression of HGF in these cells. Recombinant HGF as well as basophil-derived HGF induced endothelial cell migration in a scratch wound assay, and these effects of HGF were reverted by an anti-HGF antibody as well as by pharmacologic c-Met inhibitors. In addition, anti-HGF and c-Met inhibitors were found to suppress the spontaneous growth of KU812 cells, suggesting autocrine growth regulation. Together, HGF is a BCR-ABL1-independent angiogenic and autocrine growth regulator in CML. Basophils are a unique source of HGF in these patients and may play a more active role in disease-associated angiogenesis and disease progression than has so far been assumed. Our data also suggest that HGF and c-Met are potential therapeutic targets in CML.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 7, July 2012, Pages 572-584, IN7-IN10
Journal: Neoplasia - Volume 14, Issue 7, July 2012, Pages 572-584, IN7-IN10
نویسندگان
Sabine Cerny-Reiterer, Viviane Ghanim, Gregor Hoermann, Karl J. Aichberger, Harald Herrmann, Leonhard Muellauer, Andreas Repa, Christian Sillaber, Andrew F. Walls, Matthias Mayerhofer, Peter Valent,