Bone morphogenetic proteins and receptors are over-expressed in bone-marrow cells of multiple myeloma patients and support myeloma cells by inducing ID genes.
We assessed the expression pattern and clinical relevance of BMPs and related molecules in multiple myeloma (MM). MM bone-marrow samples (n=32) had increased BMP4, BMP6, ACVR1 and ACVR2A, and decreased NOG expression compared with controls (n=15), with BMP6 having the highest sensitivity/specificity. Within MM bone-marrow, the source of BMPs was mainly CD138(+) plasma-cell population, and BMP6 and ACVR1 expression correlated with plasma-cell percentage. Using myeloma cell lines NCI H929 and Thiel we showed that BMPs induced ID1, ID2 and IL6, and suppressed CDKN1A and BAX gene expression, and BAX protein expression. Finally, BMPs partially protected myeloma cells from bortezomib- and TRAIL-induced apoptosis. We concluded that BMPs may be involved in MM pathophysiology and serve as myeloma cell biomarkers.
Grcević
Danka
D
Department of Physiology and Immunology, University of Zagreb, School of Medicine, Zagreb, Croatia. dgrcevic@mef.hr
Kusec
Rajko
R
Kovacić
Natasa
N
Lukić
Anita
A
Lukić
Ivan Kresimir
IK
Ivcević
Sanja
S
Nemet
Damir
D
Seiwerth
Ranka Serventi
RS
Ostojić
Slobodanka Kolonić
SK
Croucher
Peter I
PI
Marusić
Ana
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics* / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D051796:Inhibitor of Differentiation Proteins; D052004:Bone Morphogenetic Protein Receptors