How Biophysical Forces Regulate Human B Cell Lymphomas
Integrins
QH301-705.5
Microfluidics
Receptors, Antigen, B-Cell
Apoptosis
Article
Mice
03 medical and health sciences
Mice, Inbred NOD
Cell Line, Tumor
Tumor Microenvironment
Animals
Humans
Biology (General)
RNA, Small Interfering
0303 health sciences
Up-Regulation
src-Family Kinases
Doxorubicin
Cytokines
RNA Interference
Lymphoma, Large B-Cell, Diffuse
Shear Strength
CD79 Antigens
Signal Transduction
DOI:
10.1016/j.celrep.2018.03.069
Publication Date:
2018-04-10T15:45:00Z
AUTHORS (10)
ABSTRACT
The role of microenvironment-mediated biophysical forces in human lymphomas remains elusive. Diffuse large B cell lymphomas (DLBCLs) are heterogeneous tumors, which originate from highly proliferative germinal center B cells. These tumors, their associated neo-vessels, and lymphatics presumably expose cells to particular fluid flow and survival signals. Here, we show that fluid flow enhances proliferation and modulates response of DLBCLs to specific therapeutic agents. Fluid flow upregulates surface expression of B cell receptors (BCRs) and integrin receptors in subsets of ABC-DLBCLs with either CD79A/B mutations or WT BCRs, similar to what is observed with xenografted human tumors in mice. Fluid flow differentially upregulates signaling targets, such as SYK and p70S6K, in ABC-DLBCLs. By selective knockdown of CD79B and inhibition of signaling targets, we provide mechanistic insights into how fluid flow mechanomodulates BCRs and integrins in ABC-DLBCLs. These findings redefine microenvironment factors that regulate lymphoma-drug interactions and will be critical for testing targeted therapies.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (48)
CITATIONS (35)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....