Murine neuronal progenitor cells are preferentially recruited to tumor vasculature via alpha4-integrin and SDF-1alpha-dependent mechanisms.
Recent studies have described neuronal progenitor cell recruitment to tumors in vivo, however, the mechanisms mediating this recruitment are not yet understood. When C17.2 murine neuronal progenitors stably expressing luciferase (C17.2-luc) were adoptively transferred into mice carrying subcutaneous Lewis lung carcinomas they accumulated at 1% injected dose/g of tumor tissue. C17.2-luc demonstrated significantly greater accumulation and transmigration on tumor-derived endothelium (TEC) than on normal endothelium under physiologically relevant flow conditions. Function blocking of alpha4-integrin reduced recruitment of C17.2-luc cells to normal endothelium but not to TEC, however, function blocking of SDF-1alpha reduced overall accumulation of C17.2-luc on TEC and specifically reduced transendothelial migration. Together, these data suggest that recruitment of C17.2-luc cells to TEC is mediated via SDF-1alpha/CXCR4 activation that results in modification of alpha4-integrin and results in improved recruitment of C17.2-luc cells.
Allport
Jennifer R
JR
Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. jennifer_allport@hms.harvard.edu
Shinde Patil
Vivek R
VR
Weissleder
Ralph
R
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000503:physiopathology*; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004727:Endothelium / Q000166:cytology; D039441:Integrin alpha4 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009474:Neurons; D019718:Receptors, CXCR4 / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D017154:Stromal Cells
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D039441:Integrin alpha4