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HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase.
Oncogene 2014; 33(38):4643-52O

Abstract

Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase. The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens. Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown. HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase activity and significantly decreased tumorigenicity and metastatic capability in orthotopically xenografted mice. These results suggest that during the progression of human PCa, matriptase activity is primarily controlled by HAI-2 expression. The imbalance between HAI-2 and matriptase expression led to matriptase activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis.

Authors+Show Affiliations

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.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.1] Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan [2] Investigation Bureau, Ministry of Justice, Taipei, Taiwan.Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA.Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA.Agricultural Biotechnology Research Center, Academia Sinica, 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

24121274

Citation

Tsai, C-H, et al. "HAI-2 Suppresses the Invasive Growth and Metastasis of Prostate Cancer Through Regulation of Matriptase." Oncogene, vol. 33, no. 38, 2014, pp. 4643-52.
Tsai CH, Teng CH, Tu YT, et al. HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase. Oncogene. 2014;33(38):4643-52.
Tsai, C. H., Teng, C. H., Tu, Y. T., Cheng, T. S., Wu, S. R., Ko, C. J., ... Lee, M. S. (2014). HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase. Oncogene, 33(38), pp. 4643-52. doi:10.1038/onc.2013.412.
Tsai CH, et al. HAI-2 Suppresses the Invasive Growth and Metastasis of Prostate Cancer Through Regulation of Matriptase. Oncogene. 2014 Sep 18;33(38):4643-52. PubMed PMID: 24121274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase. AU - Tsai,C-H, AU - Teng,C-H, AU - Tu,Y-T, AU - Cheng,T-S, AU - Wu,S-R, AU - Ko,C-J, AU - Shyu,H-Y, AU - Lan,S-W, AU - Huang,H-P, AU - Tzeng,S-F, AU - Johnson,M D, AU - Lin,C-Y, AU - Hsiao,P-W, AU - Lee,M-S, Y1 - 2013/10/14/ PY - 2012/02/10/received PY - 2013/08/19/revised PY - 2013/09/02/accepted PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2014/11/13/medline SP - 4643 EP - 52 JF - Oncogene JO - Oncogene VL - 33 IS - 38 N2 - Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase. The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens. Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown. HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase activity and significantly decreased tumorigenicity and metastatic capability in orthotopically xenografted mice. These results suggest that during the progression of human PCa, matriptase activity is primarily controlled by HAI-2 expression. The imbalance between HAI-2 and matriptase expression led to matriptase activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/24121274/HAI_2_suppresses_the_invasive_growth_and_metastasis_of_prostate_cancer_through_regulation_of_matriptase_ L2 - http://dx.doi.org/10.1038/onc.2013.412 DB - PRIME DP - Unbound Medicine ER -