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Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer.
Br J Cancer 2018; 119(7):1-9BJ

Abstract

BACKGROUND

Tissue kallikrein-related peptidases 4, 5, 6 and 7 (KLK4-7) strongly increase the malignancy of ovarian cancer cells. Deciphering their downstream effectors, we aimed at finding new potential prognostic biomarkers and treatment targets for ovarian cancer patients. KLK4-7-transfected (OV-KLK4-7) and vector-control OV-MZ-6 (OV-VC) ovarian cancer cells were established to select differentially regulated factors.

METHODS

With three independent approaches, PCR arrays, genome-wide microarray and proteome analyses, we identified 10 candidates (MSN, KRT19, COL5A2, COL1A2, BMP5, F10, KRT7, JUNB, BMP4, MMP1). To determine differential protein expression, we performed western blot analyses, immunofluorescence and immunohistochemistry for four candidates (MSN, KRT19, KRT7, JUNB) in cells, tumour xenograft and patient-derived tissues.

RESULTS

We demonstrated that KLK4-7 clearly regulates expression of MSN, KRT19, KRT7 and JUNB at the mRNA and protein levels in ovarian cancer cells and tissues. Protein expression of the top-upregulated effectors, MSN and KRT19, was investigated by immunohistochemistry in patients afflicted with serous ovarian cancer and related to KLK4-7 immunoexpression. Significant positive associations were found for KRT19/KLK4, KRT19/KLK5 and MSN/KLK7.

CONCLUSION

These findings imply that KLK4-7 exert key modulatory effects on other cancer-related genes and proteins in ovarian cancer. These downstream effectors of KLK4-7, MSN and KRT19 may represent important therapeutic targets in serous ovarian cancer.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.Department of Pathology, Technical University of Munich, Munich, Germany.Medizinisches Labor Ostsachsen, Dresden, Germany.Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany. BIOSS Centre of Biological Signaling Studies, University of Freiburg, Freiburg, Germany.Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, Brisbane, QLD, Australia. Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia.Australian Prostate Cancer Research Centre-Queensland, Translational Research Institute, Brisbane, QLD, Australia. Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia.Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia. d.loessner@qmul.ac.uk. Barts Cancer Institute, Queen Mary University of London, London, UK. d.loessner@qmul.ac.uk.

Pub Type(s)

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

Language

eng

PubMed ID

30287916

Citation

Wang, Ping, et al. "Kallikrein-related Peptidases 4, 5, 6 and 7 Regulate Tumour-associated Factors in Serous Ovarian Cancer." British Journal of Cancer, vol. 119, no. 7, 2018, pp. 1-9.
Wang P, Magdolen V, Seidl C, et al. Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer. Br J Cancer. 2018;119(7):1-9.
Wang, P., Magdolen, V., Seidl, C., Dorn, J., Drecoll, E., Kotzsch, M., ... Loessner, D. (2018). Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer. British Journal of Cancer, 119(7), pp. 1-9. doi:10.1038/s41416-018-0260-1.
Wang P, et al. Kallikrein-related Peptidases 4, 5, 6 and 7 Regulate Tumour-associated Factors in Serous Ovarian Cancer. Br J Cancer. 2018;119(7):1-9. PubMed PMID: 30287916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer. AU - Wang,Ping, AU - Magdolen,Viktor, AU - Seidl,Christof, AU - Dorn,Julia, AU - Drecoll,Enken, AU - Kotzsch,Matthias, AU - Yang,Feng, AU - Schmitt,Manfred, AU - Schilling,Oliver, AU - Rockstroh,Anja, AU - Clements,Judith Ann, AU - Loessner,Daniela, Y1 - 2018/10/05/ PY - 2018/04/24/received PY - 2018/08/16/accepted PY - 2018/08/08/revised PY - 2018/10/6/pubmed PY - 2019/8/27/medline PY - 2018/10/6/entrez SP - 1 EP - 9 JF - British journal of cancer JO - Br. J. Cancer VL - 119 IS - 7 N2 - BACKGROUND: Tissue kallikrein-related peptidases 4, 5, 6 and 7 (KLK4-7) strongly increase the malignancy of ovarian cancer cells. Deciphering their downstream effectors, we aimed at finding new potential prognostic biomarkers and treatment targets for ovarian cancer patients. KLK4-7-transfected (OV-KLK4-7) and vector-control OV-MZ-6 (OV-VC) ovarian cancer cells were established to select differentially regulated factors. METHODS: With three independent approaches, PCR arrays, genome-wide microarray and proteome analyses, we identified 10 candidates (MSN, KRT19, COL5A2, COL1A2, BMP5, F10, KRT7, JUNB, BMP4, MMP1). To determine differential protein expression, we performed western blot analyses, immunofluorescence and immunohistochemistry for four candidates (MSN, KRT19, KRT7, JUNB) in cells, tumour xenograft and patient-derived tissues. RESULTS: We demonstrated that KLK4-7 clearly regulates expression of MSN, KRT19, KRT7 and JUNB at the mRNA and protein levels in ovarian cancer cells and tissues. Protein expression of the top-upregulated effectors, MSN and KRT19, was investigated by immunohistochemistry in patients afflicted with serous ovarian cancer and related to KLK4-7 immunoexpression. Significant positive associations were found for KRT19/KLK4, KRT19/KLK5 and MSN/KLK7. CONCLUSION: These findings imply that KLK4-7 exert key modulatory effects on other cancer-related genes and proteins in ovarian cancer. These downstream effectors of KLK4-7, MSN and KRT19 may represent important therapeutic targets in serous ovarian cancer. SN - 1532-1827 UR - https://www.unboundmedicine.com/medline/citation/30287916/Kallikrein_related_peptidases_4_5_6_and_7_regulate_tumour_associated_factors_in_serous_ovarian_cancer_ L2 - http://dx.doi.org/10.1038/s41416-018-0260-1 DB - PRIME DP - Unbound Medicine ER -