Evidence of a bi-phasic effect of thrombospondin-1 on angiogenesis.
Contradictory results have been reported regarding the association between vascularity (used as an index of angiogenesis) and thrombospondin-1 (TSP-1) in human tumours. In previous studies, the reported association was based on the estimated average TSP-1 value per tumour, with a sufficient number of specimens collectively analysed per tumour type. Given the extent of intra-tumour heterogeneity, we determined the association between TSP-1 and vascularity within individual specimens, based on the average values of TSP-1 and vascularity in 10-20 pre-selected areas per tumour. Cells expressing TSP-1 mRNA were visualised by in situ hybridisation and quantified by point counting. Vascularity was quantified by point counting and vessel density of von Willebrand Factor-positive vessels. In 10 ductal breast carcinomas, a direct correlation between TSP-1 and vascularity was found in 4 tumours, no correlation in 3 and an inverse correlation in 3. The effect of TSP-1 on endothelial cell migration in vitro was assessed in the Boyden chamber assay. TSP-1 stimulated cell migration at low concentrations (0.1-10 microg/ml) and was inhibitory at high concentrations (25-100 microg/ml). These results suggest that TSP-1 may elicit a concentration-dependent, bi-phasic, effect on angiogenesis.
Motegi
Katsumi
K
Unit of Cell and Molecular Biology, Dental School, University of Dundee, Dundee DD1 4HR, Scotland.
Harada
Koji
K
Pazouki
Sima
S
Baillie
Robin
R
Schor
Ana M
AM
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012720:Severity of Illness Index; D013194:Staining and Labeling; D013223:Statistics as Topic; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000032:analysis / Q000187:drug effects
D012333:RNA, Messenger; D019700:Thrombospondin 1; D014841:von Willebrand Factor