Migration and invasion of human prostate cancer cells is related to expression of VEGF and its receptors.
BACKGROUND
Vascular endothelial growth factor (VEGF) and its receptors are becoming of increasing interest as major regulators of cancer cell growth and metastases. VEGF is expressed by many cancer cells including most prostatic carcinomas. Recently it has also been shown that the VEGF receptors are also expressed by prostate cancer cells and it has been suggested that there may be autocrine regulatory loops that are important in the development and progression of the disease. To date, however, there have only been descriptive studies of expression without correlation of the findings with possible pathophysiologic effects. The present studies were done to determine if there is a correlation between expression of VEGF receptors and the ability of human prostate cancer cells to invade and migrate in vitro.


METHODS
Using RT-PCR we examined the expression of VEGF and its receptors, KDR, Flt-1, NP-1 and NP-2, in 8 human prostate cancer cell lines and then correlated the expression patterns with the ability of these cell lines to invade and migrate through membranes in a modified Boyden Chamber assay in the presence and absence of VEGF.


RESULTS
Six of the 8 cell lines expressed VEGF. None expressed the Flt-1 receptor and only 2 expressed KDR. The most commonly expressed VEGF receptor was NP-1 (5 of 8 cell lines) and its expression was strongly, and negatively, correlated with the ability of these cell lines to invade and migrate in the assay system used. Cell lines expressing NP-1 had low levels of migration both with and without VEGF compared to those not expressing NP-1.


CONCLUSIONS
These studies suggest that variable expression of VEGF receptors in prostate cancer, particularly NP-1, may have important consequences for cell growth, invasion and metastases in this disease.
Qi
Lin
L
University of Colorado Health Sciences Center, Division of Medical Oncology-B171, 4200 East 9th Avenue, Denver, Colorado, USA.
Robinson
William A
WA
Brady
Benjamin M
BM
Glode
L Michael
LM
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D039942:Neuropilin-1 / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000494:pharmacology
D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor