Angiotropism of human prostate cancer cells: implications for extravascular migratory metastasis.
OBJECTIVE
To report several samples of invasive human prostate cancer showing angiotropism, and to use human prostate cancer cells stably expressing green fluorescence protein (GFP) in in vitro and in vivo models to assess the dissemination pathway of prostate cancer cells.


METHODS
Malignant melanoma and prostate carcinoma cells can migrate along anatomical structures such as nerves; previous studies showed that melanoma cells can be perivascular, on the outside of the endothelium, i.e. they are angiotropic, which suggests the hypothesis that melanoma cells also may migrate along vascular channels, termed 'extravascular migratory metastasis' (EVMM). Thus we examined histologically 10 human prostatic carcinoma specimens for the presence of angiotropism. In vitro, the PC-3 prostate cancer cells were co-cultures with capillary-like structures. In vivo, PC-3 cells were implanted on the chick chorio-allantoic membrane (CAM).


RESULTS
Histologically, in all 10 cases, angiotropism was detected at least focally within the tumour or at the advancing front of the tumour. In vitro, the PC-3 cells spread along the external surface of the vascular tubules; in vivo, PC-3 cells formed a cuff around some vessels a few millimetres beyond the tumour, showing angiotropism. Histopathology of the CAM confirmed the perivascular location of tumour cells and the absence of tumour cells within the vessel lumina.


CONCLUSIONS
The presence of angiotropic tumour cells in human invasive prostate cancers, associated with the angiotropism of GFP prostate cancer cells cultivated in vitro and in vivo in angiogenic models, raises the possibility that some prostate tumour cells may migrate along the external surface of vessels as a mechanism of spread, i.e. EVMM.
Lugassy
Claire
C
Department of Pathology, University of Miami School of Medicine/Jackson Memorial Hospital, Miami, FL, USA.
Vernon
Stephen E
SE
Warner
John W
JW
Le
Carter Q
CQ
Manyak
Michael
M
Patierno
Stephen R
SR
Barnhill
Raymond L
RL
D002465:Cell Movement; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D014407:Tumor Cells, Cultured
D049452:Green Fluorescent Proteins