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

Daotai Nie, Jeffrey Nemeth, Yan Qiao, Alex Zacharek, Li Li, Kenny Hanna, Keqin Tang, Gilda G. Hillman, Michael L. Cher, David Grignon, Kenneth V. Honn

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)657-663
Number of pages7
JournalClinical and Experimental Metastasis
Volume20
Issue number7
DOIs
StatePublished - 2003
Externally publishedYes

Fingerprint

Arachidonate 12-Lipoxygenase
Prostate
Carcinoma
Vitronectin
Collagen Type IV
Neoplasms
Neoplasm Metastasis
Collagen Type I
Fibronectins
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Bone and Bones
Adhesiveness
Lipoxygenase Inhibitors
SCID Mice

Keywords

  • 12-lipoxygenase
  • Adhesion
  • Cell spreading
  • Human prostate adenocarcinoma
  • Invasion
  • Metastasis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase. / Nie, Daotai; Nemeth, Jeffrey; Qiao, Yan; Zacharek, Alex; Li, Li; Hanna, Kenny; Tang, Keqin; Hillman, Gilda G.; Cher, Michael L.; Grignon, David; Honn, Kenneth V.

In: Clinical and Experimental Metastasis, Vol. 20, No. 7, 2003, p. 657-663.

Research output: Contribution to journalArticle

Nie, D, Nemeth, J, Qiao, Y, Zacharek, A, Li, L, Hanna, K, Tang, K, Hillman, GG, Cher, ML, Grignon, D & Honn, KV 2003, 'Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase', Clinical and Experimental Metastasis, vol. 20, no. 7, pp. 657-663. https://doi.org/10.1023/A:1027302408187
Nie, Daotai ; Nemeth, Jeffrey ; Qiao, Yan ; Zacharek, Alex ; Li, Li ; Hanna, Kenny ; Tang, Keqin ; Hillman, Gilda G. ; Cher, Michael L. ; Grignon, David ; Honn, Kenneth V. / Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase. In: Clinical and Experimental Metastasis. 2003 ; Vol. 20, No. 7. pp. 657-663.
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abstract = "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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AU - Nemeth, Jeffrey

AU - Qiao, Yan

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AU - Hanna, Kenny

AU - Tang, Keqin

AU - Hillman, Gilda G.

AU - Cher, Michael L.

AU - Grignon, David

AU - Honn, Kenneth V.

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