Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase
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.
Tài liệu tham khảo
Honn KV, Tang DG, Gao X et al. 12-lipoxygenases and 12(s)-HETE: Role in cancer metastasis. Cancer Metast Rev 1994; 13: 365–96.
Gao X, Grignon DJ, Chbihi T et al. Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. Urology 1995; 46: 227–37.
Ding XZ, Iversen P, Cluck MWet al. Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells. Biochem Biophys Res Comm 1999; 261: 218–23.
Connolly JM, Rose DP. Enhanced angiogenesis and growth of 12-lipoxygenase gene-transfected MCF-7 human breast cancer cells in athymic nude mice. Cancer Lett 1998; 132: 107–12.
Chen YQ, Duniec ZM, Liu B et al. Endogenous 12(S)-HETE production by tumor cells and its role in metastasis. Cancer Res 1994; 54: 1574–9.
Wong BC, Wang WP, Cho CH et al. 12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells. Carcinogenesis 2001; 22: 1349–1354.
Hong SH, Avis I, Vos MD et al. Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors. Cancer Res 1999; 59: 2223–8.
Nie D, Hillman GG, Gedded T et al. Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates angiogenesis and tumor growth. Cancer Res 1998; 58: 4047–51.
Liu B, Marnett LJ, Chaudhary A et al. Biosynthesis of 12(S)-Hydroxyeicosatetraenoic acid by B16 amelanotic melanoma cells is a determinant of their metastatic potential. Lab Invest 1994; 70: 314–23.
Nie D, Tang K, Diglio C, Honn KV. Eicosanoid regulation of angiogenesis: Role of endothelial arachidonate 12-lipoxygenase. Blood 2000; 95: 2304–11.
Nemeth JA, Harb JF, Barroso U Jr et al. Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone. Cancer Res 1999; 59: 1987–93.
Heasley LE, Thaler S, Nicks M et al. Induction of cytosolic phospholipase A2 by oncogenic Ras in human non-small cell lung cancer. J Biol Chem 1997; 272: 14501–4.
Kelavkar UP, Nixon JB, Cohen C et al. Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis. Carcinogenesis 2001; 22: 1765–73.
Liu B, Timar J, Howlett J, Honn KV. Lipoxygenase metabolites of arachidonic and linolic acids modulate the adhesion of tumor cells to endothelium via regulation of protein kinase C. Cell Regul 1991; 2: 1045–55.
Honn KV, Grossi IM, Diglio CA et al. Enhanced tumor cell adhesion to the subendothelial matrix resulting from 12(S)-HETE induced endothelial cell retraction. FASEB J 1989; 3: 2285–93.
Liu B, Maher RJ, Hannun YA et al. 12(S)-HETE enhancement of prostate tumor cell invasion: Selective role of PKCa. J Natl Cancer Inst 1994; 86: 1145–51.
Timar J, Silletti S, Bazaz R, Honn KV. Regulation of melanoma-cell motility by the lipoxygenase metabolite 12(S)-HETE. Int J Cancer 1993; 55: 1003–10.
Ulbricht B, Hagmann W, Ebert W, Spiess E. Differential secretion of cathepsins B and L from normal and tumor human lung cells stimulated by 12(S)-hydroxy-eicosatetraenoic acid. Exp Cell Res 1996; 226: 255–63.
Honn KV, Timár J, Rozhin J et al. A lipoxygenase metabolite, 12(S)-HETE, stimulates protein kinase C-mediated release of cathepsin B from malignant cells. Exp Cell Res 1994; 214: 120–30.
Timar J, Bazaz R, Kimler V et al. Immunomorphological characterization and effects of 12-(S)-HETE on a dynamic intracellular pool of the alpha IIb beta 3-integrin in melanoma cells. J Cell Sci 1995; 108: 2175–86.
Timar J, Chen YQ, Liu B et al. The lipoxygenase metabolite 12(S)-HETE promotes cytoadhesion moecule aIIbß3 mediated tumor cell spreading on fibronectin. Int J Cancer 1992; 52: 594–603.
Liu XH, Connolly JM, Rose DP. Eicosanoids as mediators of linoleic acid-stimulated invasion and type IV collagenase production by a metastatic human breast cancer cell line. Clin Exp Metastasis 1996; 14: 145-52.
Nie D, Ishikawa Y, Yoshimori T et al. Retinoic acid treatment elevates matrix metalloproteinase-2 protein and mRNA levels in avian growth plate chondrocyte cultures. J Cell Biochem 1998; 68: 90–9.
Dong Z, Nemeth J A, Cher ML et al. Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells. Int J Cancer 2001; 93: 507–15.
Rice RL, Tang DG, Haddad M et al. 12(S)-Hydroxyeicosatetraenoic acid increases the actin microfilament content in B16a melanoma cells: A protein kinase-dependent process. Int J Cancer 1998; 77: 271–8.
Termine JD, Robey PG. Bone matrix proteins and the mineralization process. In Whyte MP (ed): Primer on the Metabolic Bone Diseases and Disorders ofMineralMetabolism. American Society for Bone and Mineral Research. Philadelphia: Lippincott-Raven 1996; 24–8.