Journal of Gastric Cancer

  • 제18권4호
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  • Pages.356-367
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  • 2018
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  • 2093-582X(pISSN)
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  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
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KLK6 Promotes Growth, Migration, and Invasion of Gastric Cancer Cells

  • Zhu, Shengxing (Department of Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Shi, Jihua (Department of Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Shanfeng (School of Basic Medicine, Zhengzhou University) ;
  • Li, Zhen (Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University)
  • 투고 : 2018.09.03
  • 심사 : 2018.11.04
  • 발행 : 2018.12.31
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초록

Purpose: Kallikrein (KLK) proteases are hormone-like signaling molecules with critical functions in different cancers. This study investigated the expression of KLK6 in gastric cancer and its potential role in the growth, migration, and invasion of gastric cancer cells. Materials and Methods: In this study, we compared protein levels of KLK6, vascular endothelial growth factor (VEGF), and matrix metallopeptidase (MMP) 9 in normal gastric epithelial and gastric cancer cell lines by western blot. Fluorescence-activated cell sorting was employed to sort 2 clones of SGC-7901 cells with distinct KLK6 expression, namely, KLK6-high ($KLK6^{high}$) and KLK6-low ($KLK6^{low}$), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients. Results: The expression levels of KLK6, VEGF, and MMP 9, were significantly higher in the gastric cancer cell lines SGC-7901, BGC-823, MKN-28, and MGC-803 than in the normal gastric epithelial cell line GES-1. Compared to $KLK6^{low}$ cells, $KLK6^{high}$ cells showed enhanced viability, colony-forming ability, migration, and invasion potential in vitro. Importantly, immunohistochemical analysis of a human gastric cancer tissue cohort revealed that the staining for KLK6, VEGF, and MMP9 was markedly stronger in the cancerous tissues than in the adjacent normal tissues. KLK6 expression also correlated with that of VEGF and MMP9 expression, as well as several key clinicopathological parameters. Conclusions: Together, these results suggest an important role for KLK6 in human gastric cancer progression.

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참고문헌

  1. Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001;22:184-204.
  2. Borgono CA, Diamandis EP. The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer 2004;4:876-890. https://doi.org/10.1038/nrc1474
  3. Jin Y, Qu S, Tesikova M, Wang L, Kristian A, Mælandsmo GM, et al. Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer. Proc Natl Acad Sci U S A 2013;110:E2572-E2581. https://doi.org/10.1073/pnas.1304318110
  4. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317:909-916. https://doi.org/10.1056/NEJM198710083171501
  5. Nagahara H, Mimori K, Utsunomiya T, Barnard GF, Ohira M, Hirakawa K, et al. Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer. Clin Cancer Res 2005;11:6800-6806. https://doi.org/10.1158/1078-0432.CCR-05-0943
  6. Schuster R, Max N, Mann B, Heufelder K, Thilo F, Grone J, et al. Quantitative real-time RT-PCR for detection of disseminated tumor cells in peripheral blood of patients with colorectal cancer using different mRNA markers. Int J Cancer 2004;108:219-227. https://doi.org/10.1002/ijc.11547
  7. Nathalie HV, Chris P, Serge G, Catherine C, Benjamin B, Claire B, et al. High kallikrein-related peptidase 6 in non-small cell lung cancer cells: an indicator of tumour proliferation and poor prognosis. J Cell Mol Med 2009;139B:4014-4022. https://doi.org/10.1111/j.1582-4934.2009.00763.x
  8. Shan SJ, Scorilas A, Katsaros D, Diamandis EP. Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects. Br J Cancer 2007;96:362-372. https://doi.org/10.1038/sj.bjc.6603556
  9. Vakrakou A, Devetzi M, Papachristopoulou G, Malachias A, Scorilas A, Xynopoulos D, et al. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma. Biol Chem 2014;395:1105-1117.
  10. Klucky B, Mueller R, Vogt I, Teurich S, Hartenstein B, Breuhahn K, et al. Kallikrein 6 induces E-cadherin shedding and promotes cell proliferation, migration, and invasion. Cancer Res 2007;67:8198-8206. https://doi.org/10.1158/0008-5472.CAN-07-0607
  11. Kim JT, Song EY, Chung KS, Kang MA, Kim JW, Kim SJ, et al. Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer. Cancer 2011;117:2608-2619. https://doi.org/10.1002/cncr.25841
  12. Sawada K, Mitra AK, Radjabi AR, Bhaskar V, Kistner EO, Tretiakova M, et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res 2008;68:2329-2339. https://doi.org/10.1158/0008-5472.CAN-07-5167
  13. Kim TW, Lee SJ, Kim JT, Kim SJ, Min JK, Bae KH, et al. Kallikrein-related peptidase 6 induces chemotherapeutic resistance by attenuating auranofin-induced cell death through activation of autophagy in gastric cancer. Oncotarget 2016;7:85332-85348.
  14. Masoumi Moghaddam S, Amini A, Morris DL, Pourgholami MH. Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer. Cancer Metastasis Rev 2012;31:143-162. https://doi.org/10.1007/s10555-011-9337-5
  15. Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 2006;25:9-34. https://doi.org/10.1007/s10555-006-7886-9
  16. Carcas LP. Gastric cancer review. J Carcinog 2014;13:14. https://doi.org/10.4103/1477-3163.146506
  17. Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet 2016;388:2654-2664. https://doi.org/10.1016/S0140-6736(16)30354-3
  18. Lenga Ma Bonda W, Iochmann S, Magnen M, Courty Y, Reverdiau P. Kallikrein-related peptidases in lung diseases. Biol Chem 2018;399:959-971. https://doi.org/10.1515/hsz-2018-0114
  19. Kim JJ, Kim JT, Yoon HR, Kang MA, Kim JH, Lee YH, et al. Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric cancer. Tumour Biol 2012;33:731-738. https://doi.org/10.1007/s13277-011-0267-1
  20. Oikonomopoulou K, Diamandis EP, Hollenberg MD. Kallikrein-related peptidases: proteolysis and signaling in cancer, the new frontier. Biol Chem 2010;391:299-310.
  21. Sananes A, Cohen I, Shahar A, Hockla A, De Vita E, Miller AK, et al. A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering. J Biol Chem 2018;293:12663-12680. https://doi.org/10.1074/jbc.RA117.000871
  22. Sidiropoulos KG, Ding Q, Pampalakis G, White NM, Boulos P, Sotiropoulou G, et al. KLK6-regulated miRNA networks activate oncogenic pathways in breast cancer subtypes. Mol Oncol 2016;10:993-1007. https://doi.org/10.1016/j.molonc.2016.03.008

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