Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase.
Arachidonate 12-lipoxygenase (LOX) converts arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid (HETE), a bioactive lipid implicated in tumor angiogenesis, growth, and metastasis. Alteration in 12-LOX expression or activity has been reported in various carcinomas including prostate carcinoma. However, little is known about the impact of the altered expression or activity of 12-LOX on tumor metastasis. In the present study, we examined whether or not an increase in 12-LOX expression in human prostate carcinoma cells can modulate their metastatic potential. We report that increased expression of 12-LOX in PC-3 cells caused a significant change in cell adhesiveness, spreading, motility, and invasiveness. Specifically 12-LOX transfected PC-3 cells were more adhesive toward vitronectin, type I and IV collagen, but not to fibronectin or laminin, than cells transfected with control vector. Increased spreading on vitronectin, fibronectin, collagen type I and IV also was observed in 12-LOX transfected PC-3 cells when compared to control PC-3 cells. The increased spreading of 12-LOX transfected PC-3 cells was blocked by treatment with 12-LOX inhibitors, baicalein and CDC. 12-LOX transfected PC-3 cells were more invasive through Matrigel than cells transfected with control vector. In vivo, tumor cell invasion to surrounding muscle or fat tissues was more frequent in nude mice bearing s.c. tumors from 12-LOX transfected PC-3 cells than in those from control vector transfected cells. When injected via the tail vein into SCID mice with implanted human bone fragments, there was an increase in tumor metastasis to human bone by 12-LOX transfected PC-3 cells in comparison to control vector transfected cells. Taken together, our data suggest that an increase in 12-LOX expression enhances the metastatic potential of human prostate cancer cells.
Nie
Daotai
D
Department of Radiation Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan 48202, USA.
Nemeth
Jeffrey
J
Qiao
Yan
Y
Zacharek
Alex
A
Li
Li
L
Hanna
Kenny
K
Tang
Keqin
K
Hillman
Gilda G
GG
Cher
Michael L
ML
Grignon
David J
DJ
Honn
Kenneth V
KV
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001859:Bone Neoplasms / Q000556:secondary*; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D001092:Arachidonate 12-Lipoxygenase