SDF1/CXCL12 is involved in recruitment of stem-like progenitor cells to orthotopic murine malignant mesothelioma spheroids.
OBJECTIVE
Tumor progression is influenced by the microenvironment. We found stem cells are recruited to malignant mesothelioma spheroids. We aimed to determine if stem cell recruitment depends on the chemokine SDF1, and if inhibition of the cognate receptor CXCR4 affects tumor growth.


METHODS
The kinetics of stem cell recruitment was determined using immunofluorescence staining, BrdU incorporation and eGFP transgenic mice. Chemokines were identified using PCR array. Inhibitors of CXCR4 were used to determine the effect on cell migration and tumor progression.


RESULTS
The increasing number of stem cells found in tumor spheroids over time is attributed to cell recruitment. Stem cell migration in vitro was enhanced by exogenous SDF1 and abrogated by CXCR4 inhibition and. CXCR4 inhibition reduced tumor burden in vivo.


CONCLUSIONS
SDF1 is a candidate chemokine for recruitment of stem cells to malignant peritoneal mesothelioma and a potential target for therapy.
Lau
Bonnie W
BW
Department of Pathology and Laboratory Medicine, Brown University, Box G-8235, Providence, RI 02912, USA. Bonnie_Lau@brown.edu
Kane
Agnes B
AB
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001596:Benzylamines; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008565:Membrane Proteins / Q000032:analysis; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008654:Mesothelioma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018874:Spheroids, Cellular / Q000473:pathology*
D000950:Antigens, Ly; D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019718:Receptors, CXCR4; C088327:plerixafor