Neural cell adhesion molecule modulates mesenchymal stromal cell migration via activation of MAPK/ERK signaling.
Mesenchymal Stromal Cells (MSCs) represent promising tools for cellular therapy owing to their multipotentiality and ability to localize to injured, inflamed sites and tumor. Various approaches to manipulate expression of MSC surface markers, including adhesion molecules and chemokine receptors, have been explored to enhance homing of MSCs. Recently, Neural Cell Adhesion Molecule (NCAM) has been found to be expressed on MSCs yet its function remains largely elusive. Herein, we show that bone marrow-derived MSCs from NCAM deficient mice exhibit defective migratory ability and significantly impaired adipogenic and osteogenic differentiation potential. We further explore the mechanism governing NCAM mediated migration of MSCs by showing the interplay between NCAM and Fibroblast Growth Factor Receptor (FGFR) induces activation of MAPK/ERK signaling, thereby the migration of MSCs. In addition, re-expression of NCAM180, but not NCAM140, could restore the defective MAPK/ERK signaling thereby the migration of NCAM deficient MSCs. Finally, we demonstrate that NCAM180 expression level could be manipulated by pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-α treatment. Overall, our data reveal the vital function of NCAM in MSCs migration and differentiation thus raising the possibility of manipulating NCAM expression to enhance homing and therapeutic potential of MSCs in cellular therapy.
School of Biological Sciences, Nanyang Technological University, #60 Nanyang Drive, Singapore 637551, Singapore.
Yu
Y
Shi
Yin-Yan
YY
Xia
Lei
L
Wang
Rui
R
Liu
King-Shung
KS
Khoo
Zhi-Wei
ZW
Feng
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019002:CD56 Antigen / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019002:CD56 Antigen; C501063:Ncam1 protein, mouse; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases