Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal and malignant cell origin.
BACKGROUND
Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis.


METHODS
VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy.


RESULTS
VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy.


CONCLUSIONS
Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium.
Babiker
Adil A
AA
Rudbeck Laboratory C5, Department of Oncology, Uppsala, Sweden.
Magnusson
Peetra U
PU
Ronquist
Gunnar
G
Nilsson
Bo
B
Ekdahl
Kristina Nilsson
KN
D000704:Analysis of Variance; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D043169:Endostatins / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D022142:Secretory Vesicles / Q000378:metabolism* / Q000473:pathology; D012661:Semen / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043169:Endostatins; D019332:Endothelin-1; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A