A HGF/cMET Autocrine Loop Is Operative in Multiple Myeloma Bone Marrow Endothelial Cells and May Represent a Novel Therapeutic Target
| العنوان: | A HGF/cMET Autocrine Loop Is Operative in Multiple Myeloma Bone Marrow Endothelial Cells and May Represent a Novel Therapeutic Target |
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| المؤلفون: | Daniele Vergara, Arianna Ferrucci, Michele Moschetta, Ivana Catacchio, Antonio Giovanni Solimando, Vito Racanelli, Dominga Latorre, Maria Antonia Frassanito, Antonia Rizzello, A Zito, Antonella Caivano, Angelo Vacca, Roberto Ria, Michele Maffia, Simona Berardi, Domenico Ribatti, Eugenio Maiorano, Paolo Ditonno |
| المساهمون: | Arianna, Ferrucci, Michele, Moschetta, Maria Antonia, Frassanito, Simona, Berardi, Ivana, Catacchio, Roberto, Ria, Vito, Racanelli, Antonella, Caivano, Antonio Giovanni, Solimando, Vergara, Daniele, Maffia, Michele, Dominga, Latorre, Rizzello, Antonia, Alfredo, Zito, Paolo, Ditonno, Eugenio, Maiorano, Domenico, Ribatti, Angelo, Vacca |
| المصدر: | Clinical Cancer Research. 20:5796-5807 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Proteomics, Cancer Research, Indoles, Proteome, Angiogenesis, Gene Expression, Angiogenesis Inhibitors, Monoclonal Gammopathy of Undetermined Significance, Piperazines, Tyrosine-kinase inhibitor, tyrosine kinase receptor mesenchymal epithelial transition factor, Cell Movement, immune system diseases, hemic and lymphatic diseases, Molecular Targeted Therapy, Multiple myeloma, Aged, 80 and over, Sulfonamides, Neovascularization, Pathologic, Hepatocyte Growth Factor, Bortezomib, bortezomib, neutralizing antibody, Middle Aged, Proto-Oncogene Proteins c-met, Autocrine Communication, medicine.anatomical_structure, Oncology, Cytokines, Female, Hepatocyte growth factor, Multiple Myeloma, medicine.drug, Adult, medicine.drug_class, lenalidomide, Bone Marrow Cells, medicine, Humans, Aged, Lenalidomide, business.industry, Endothelial Cells, medicine.disease, Immunology, Cancer research, Bone marrow, business, Monoclonal gammopathy of undetermined significance |
| الوصف: | Purpose: The aim of this study was to investigate the angiogenic role of the hepatocyte growth factor (HGF)/cMET pathway and its inhibition in bone marrow endothelial cells (EC) from patients with multiple myeloma versus from patients with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (control group). Experimental Design: The HGF/cMET pathway was evaluated in ECs from patients with multiple myeloma (multiple myeloma ECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies, or on refractory phase to these drugs; in ECs from patients with MGUS (MGECs); and in those patients from the control group. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on multiple myeloma ECs' angiogenic activities were studied in vitro and in vivo. Results: Multiple myeloma ECs express more HGF, cMET, and activated cMET (phospho (p)-cMET) at both RNA and protein levels versus MGECs and control ECs. Multiple myeloma ECs are able to maintain the HGF/cMET pathway activation in absence of external stimulation, whereas treatment with anti-HGF and anti-cMET neutralizing antibodies (Ab) is able to inhibit cMET activation. The cMET pathway regulates several multiple myeloma EC activities, including chemotaxis, motility, adhesion, spreading, and whole angiogenesis. Its inhibition by SU11274 impairs these activities in a statistically significant fashion when combined with bortezomib or lenalidomide, both in vitro and in vivo. Conclusions: An autocrine HGF/cMET loop sustains multiple myeloma angiogenesis and represents an appealing new target to potentiate the antiangiogenic management of patients with multiple myeloma. Clin Cancer Res; 20(22); 5796–807. ©2014 AACR. |
| وصف الملف: | ELETTRONICO |
| تدمد: | 1557-3265 1078-0432 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a563b512babc96a41abd01a4563182bb https://doi.org/10.1158/1078-0432.ccr-14-0847 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a563b512babc96a41abd01a4563182bb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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