Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase

Springer Science and Business Media LLC - Tập 20 - Trang 657-663 - 2003
Daotai Nie1, Jeffrey Nemeth2, Yan Qiao1, Alex Zacharek1, Li Li1,3, Kenny Hanna1, Keqin Tang1, Gilda G. Hillman1, Michael L. Cher1,4, David J. Grignon4, Kenneth V. Honn1,4
1Departments of Radiation Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, USA
2Urology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, USA
3Biomide Corporation, Grosse Pointe Farms, USA
4Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, USA

Tóm tắt

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.

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