Unique biomechanical interactions between myeloma cells and bone marrow stroma cells.
We observed that BMSCs (bone marrow stromal cells) from myeloma patients (myeloma BMSCs) were significantly stiffer than control BMSCs using a cytocompression device. The stiffness of myeloma BMSCs and control BMSCs was further increased upon priming by myeloma cells. Additionally, myeloma cells became stiffer when primed by myeloma BMSCs. The focal adhesion kinase activity of myeloma cells was increased when cells were on stiffer collagen gels and on myeloma BMSCs. This change in myeloma stiffness is associated with increased colony formation of myeloma cells and FAK activation when co-cultured with stiffer myeloma BMSCs or stiffer collagen. Additionally, stem cells of RPMI8226 cells became stiffer after priming by myeloma BMSCs, with concomitant increases of stem cell colony formation. These results suggest the presence of a mechanotransduction loop between myeloma cells and myeloma BMSCs to increase the stiffness of both types of cells via FAK activation. The increase of stiffness may in turn support the growth of myeloma cells and myeloma stem cells.
Department of Pathology, The Methodist Hospital and The Methodist Hospital Research Institute, 6565 Fannin, MS205, Houston, TX 77030, USA.
Yongdong
Y
Feng
Gidon
G
Ofek
Dong Soon
DS
Choi
Jianguo
J
Wen
Jerry
J
Hu
Hong
H
Zhao
Youli
Y
Zu
Kyriacos A
KA
Athanasiou
Chung-Che
CC
Chang
D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
D051416:Focal Adhesion Protein-Tyrosine Kinases