Tags

Type your tag names separated by a space and hit enter

Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis.
Oncogene 2017; 36(32):4597-4609O

Abstract

Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1β (IL-1β) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E2 (PGE2) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Bureau of Investigation, Ministry of Justice, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28368394

Citation

Ko, C-J, et al. "Inhibition of Cyclooxygenase-2-mediated Matriptase Activation Contributes to the Suppression of Prostate Cancer Cell Motility and Metastasis." Oncogene, vol. 36, no. 32, 2017, pp. 4597-4609.
Ko CJ, Lan SW, Lu YC, et al. Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis. Oncogene. 2017;36(32):4597-4609.
Ko, C. J., Lan, S. W., Lu, Y. C., Cheng, T. S., Lai, P. F., Tsai, C. H., ... Lee, M. S. (2017). Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis. Oncogene, 36(32), pp. 4597-4609. doi:10.1038/onc.2017.82.
Ko CJ, et al. Inhibition of Cyclooxygenase-2-mediated Matriptase Activation Contributes to the Suppression of Prostate Cancer Cell Motility and Metastasis. Oncogene. 2017 08 10;36(32):4597-4609. PubMed PMID: 28368394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis. AU - Ko,C-J, AU - Lan,S-W, AU - Lu,Y-C, AU - Cheng,T-S, AU - Lai,P-F, AU - Tsai,C-H, AU - Hsu,T-W, AU - Lin,H-Y, AU - Shyu,H-Y, AU - Wu,S-R, AU - Lin,H-H, AU - Hsiao,P-W, AU - Chen,C-H, AU - Huang,H-P, AU - Lee,M-S, Y1 - 2017/04/03/ PY - 2017/02/13/received PY - 2017/02/22/accepted PY - 2017/4/4/pubmed PY - 2017/9/28/medline PY - 2017/4/4/entrez SP - 4597 EP - 4609 JF - Oncogene JO - Oncogene VL - 36 IS - 32 N2 - Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1β (IL-1β) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E2 (PGE2) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/28368394/Inhibition_of_cyclooxygenase_2_mediated_matriptase_activation_contributes_to_the_suppression_of_prostate_cancer_cell_motility_and_metastasis_ L2 - http://dx.doi.org/10.1038/onc.2017.82 DB - PRIME DP - Unbound Medicine ER -