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
PY - 2018/10/5
Y1 - 2018/10/5
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054471739&partnerID=8YFLogxK
U2 - 10.1038/s41416-018-0260-1
DO - 10.1038/s41416-018-0260-1
M3 - Article
C2 - 30287916
AN - SCOPUS:85054471739
SN - 0007-0920
VL - 119
SP - 823
EP - 831
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -
