Transforming Growth Factor β Receptor I Kinase Inhibitor Down-Regulates Cytokine Secretion and Multiple Myeloma Cell Growth in the Bone Marrow Microenvironment

2004 ◽  
Vol 10 (22) ◽  
pp. 7540-7546 ◽  
Author(s):  
Toshiaki Hayashi ◽  
Teru Hideshima ◽  
Aaron N. Nguyen ◽  
Olivier Munoz ◽  
Klaus Podar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Transforming Growth Factor Β ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell ◽  
Β Receptor

scholarly journals The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells

2011 ◽  
Vol 22 (9) ◽  
pp. 1463-1472 ◽  
Author(s):  
Kathleen E. Lambert ◽  
Huang Huang ◽  
Karthikeyan Mythreye ◽  
Gerard C. Blobe
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Myeloma Cell ◽  
Myeloma Cells ◽  
Β Receptor

Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serves as a novel suppressor of cancer progression in epithelial tumors; however, its role in hematologic malignancies is unknown. Here we demonstrate that TβRIII protein expression is decreased or lost in the majority of human multiple myeloma specimens. Functionally, restoring TβRIII expression in myeloma cells significantly inhibited cell growth, proliferation, and motility, largely independent of its ligand presentation role. In a reciprocal fashion, shRNA-mediated silencing of endogenous TβRIII expression enhanced cell growth, proliferation, and motility. Although apoptosis was not affected, TβRIII inhibited proliferation through induction of the cyclin-dependent kinase inhibitors p21 and p27. TβRIII further regulated myeloma cell adhesion, increasing homotypic myeloma cell adhesion while decreasing myeloma heterotropic adhesion to bone marrow stromal cells. Mechanistically, live cell imaging of myeloma and stroma cell cocultures revealed that TβRIII-mediated inhibition of heterotropic adhesion was associated with decreased duration of myeloma/bone marrow stromal cell interaction. These results suggest that loss of TβRIII expression during multiple myeloma progression contributes to disease progression through its functional effects on increased cell growth, proliferation, motility, and adhesion.

Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 703-705 ◽  
Author(s):  
Teru Hideshima ◽  
Masaharu Akiyama ◽  
Toshiaki Hayashi ◽  
Paul Richardson ◽  
Robert Schlossman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Cell Growth ◽  
P38 Mapk ◽  
Myeloma Cell ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Multiple Myeloma Cell ◽  
Mitogen Activated Protein

p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family which is activated by cytokines and growth factors, but its role in pathogenesis of multiple myeloma (MM) is unknown. In this study, we demonstrate that the specific p38 MAPK inhibitor VX-745 inhibits interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in bone marrow stromal cells (BMSCs), without affecting their viability. Tumor necrosis factor alpha (TNF-α)–induced IL-6 secretion in BMSCs is also inhibited by VX-745. Importantly, VX-745 inhibits both MM cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that it can inhibit paracrine MM cell growth in the BM milieu and overcome cell adhesion–related drug resistance. These studies therefore identify p38 MAPK as a novel therapeutic target to overcome drug resistance and improve patient outcome in MM.

scholarly journals Transforming growth factor-β receptor III downregulation in prostate cancer: is inhibin B a tumor suppressor in prostate?

2007 ◽  
Vol 39 (5) ◽  
pp. 329-332 ◽  
Author(s):  
Nima Sharifi ◽  
Robert J Lechleider ◽  
William L Farrar
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Invasion And Metastasis ◽  
Dual Roles ◽  
Growth Inhibitory ◽  
Β Receptor

AbstractThe transforming growth factor-β (TGF-β) pathway plays dual roles in cancer, inhibiting epithelial cell growth under normal physiologic conditions, but promoting invasion and metastasis once growth inhibitory responses are lost. Two recent papers show that TGF-β receptor III is the most common TGF-β pathway component downregulated in prostate cancer. Here, we discuss the implications of these findings and what it may mean about the biology of this disease.

Short hairpin RNA silencing of interleukin-6 in human bone marrow-derived mesenchymal stromal cells inhibits multiple myeloma cell growth

Pathology ◽  
2016 ◽  
Vol 48 ◽  
pp. S99 ◽  
Author(s):  
Hoon Koon Teoh ◽  
Pei Pei Chong ◽  
Maha Abdullah ◽  
Zamberi Sekawi ◽  
Geok Chin Tan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Growth ◽  
Stromal Cells ◽  
Interleukin 6 ◽  
Rna Silencing ◽  
Myeloma Cell ◽  
Hairpin Rna ◽  
Multiple Myeloma Cell ◽  
Short Hairpin
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