Malignant melanoma induces migration and invasion of adult mesenchymal stem cells.
OBJECTIVE
To determine if melanoma cells secrete chemotactic factors that result in the migration of multipotent stem cells.


METHODS
In vitro cell culture.


METHODS
Chemotaxis and invasion of human mesenchymal stem cells (hMSCs) was determined using the modified Boyden chamber assay. Quantification of growth factors secreted by melanoma cells (A375) was determined using enzyme-linked immunosorbent assay.


RESULTS
Conditioned A375 melanoma media caused significant migration and invasion of hMSCs compared to serum-free controls and conditioned media from normal melanocytes (P < .0001). The migratory effect appeared maximal after the A375 media was conditioned for 48 hours. Physiologically relevant concentrations of fibroblast growth factor-2 (FGF2) (90 pg/mL) secreted by A375 melanoma cells caused significant migration of hMSCs (P < .001) compared to serum-free and normal melanocyte controls. Neutralization of FGF2 inhibited the migration of hMSCs to that of the negative controls (conditioned media from normal melanocytes).


CONCLUSIONS
The melanoma tumor microenvironment may be maintained through chemotaxis and invasion of multipotent hMSCs, and this migratory effect appears to be mediated in part through secretion of FGF2 by melanoma cells.
Department of Otolaryngology-Head and Neck Surgery, University of Texas Medical Branch, Galveston, Texas, USA. tlwatts@utmb.edu
Tammara L
TL
Watts
Ruwen
R
Cui
D053687:Adult Stem Cells / Q000187:drug effects / Q000473:pathology*; D045744:Cell Line, Tumor; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology*
D002630:Chemotactic Factors; D017077:Culture Media, Conditioned