Increased stem cell factor release by hemangioma-derived endothelial cells.
BACKGROUND
Capillary hemangiomas, the most common tumors in young children, consist of proliferating capillary vessels and endothelial cells. These tumors also contain large numbers of mast cells, compared with the normal surrounding skin or tissue. We have recently shown that stem cell factor (SCF), the gene product of the murine steel locus, can act as a chemoattractant for mast cells. In this study, we investigated whether SCF might be involved in the recruitment and maintenance of mast cells in hemangiomas.


METHODS
Cultured endothelial cells derived from a murine hemangioma were compared with normal vascular endothelial cells for the ability to produce and release SCF, a mitogen for mast cells.


RESULTS
Conditioned medium from hemangioma-derived endothelial cells stimulated the proliferation of cultured mast cells. This proliferative activity was potentiated by interleukin-3. The same conditioned medium was unable to stimulate proliferation of mast cells expressing a defective receptor for SCF. The medium was also unable to stimulate proliferation when it was preincubated with neutralizing antibodies specific for SCF. Immunoprecipitation and Western blot analysis of the conditioned media from hemangioma cells and normal endothelial cells demonstrated the 31,000 molecular weight SCF in hemangioma-conditioned medium only. In addition, proliferative activity for mast cells could not be demonstrated in the conditioned medium of the normal endothelial cells, although Northern blot analysis indicated that both normal and hemangioma-derived endothelial cells express SCF mRNA. Reverse transcriptase-polymerase chain reaction techniques were used to amplify the DNA sequence coding for the proteolytic cleavage site used for release of SCF. Results indicated that both normal and hemangioma-derived endothelial cells express the same transcript for SCF.


CONCLUSIONS
Our data suggest that increased release of SCF is a property of hemangioma-derived endothelial cells that may account for the high numbers of mast cells observed in hemangioma tissue. This increased release of SCF is not due to alternate splicing of SCF transcripts by hemangioma cells.
Meininger
C J
CJ
Department of Medical Physiology, Texas A&M University Health Science Center, College Station.
Brightman
S E
SE
Kelly
K A
KA
Zetter
B R
BR
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002196:Capillaries / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D017931:DNA Primers / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006391:Hemangioma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D016298:Hematopoietic Cell Growth Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D017931:DNA Primers; D016298:Hematopoietic Cell Growth Factors; D012333:RNA, Messenger; D019089:Stem Cell Factor; D004247:DNA