Download PDF
Thromb Haemost 2009; 101(04): 741-747
DOI: 10.1160/TH08-07-0471
Cellular Proteolysis and Oncology
Schattauer GmbH

Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer

Maroulio Talieri
1   Department of Cellular Physiology, “G. Papanicolaou” Research Center of Oncology, “Saint Savas” Hospital, Athens, Greece
,
Konstantina Mathioudaki
1   Department of Cellular Physiology, “G. Papanicolaou” Research Center of Oncology, “Saint Savas” Hospital, Athens, Greece
,
Panagiotis Prezas
1   Department of Cellular Physiology, “G. Papanicolaou” Research Center of Oncology, “Saint Savas” Hospital, Athens, Greece
,
Dimitra K. Alexopoulou
1   Department of Cellular Physiology, “G. Papanicolaou” Research Center of Oncology, “Saint Savas” Hospital, Athens, Greece
,
Eleftherios P. Diamandis
2   Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
,
Dimitris Xynopoulos
3   Department of Gastroenterology, “Saint Savas” Hospital, Athens, Greece
,
Alexandros Ardavanis
4   Department of Oncology, “Saint Savas” Hospital, Athens, Greece
,
Niki Arnogiannaki
5   Department of Pathology, “Saint Savas” Hospital, Athens, Greece
,
Andreas Scorilas
6   Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece
› Author AffiliationsFinancial support: General Secretariat for Research and Technology of Greece (GSRT.109-γ) EPAN (Measure 4.3, Action 4.3.6.1γ) within the framework of “Bilateral RTD Cooperation”. The fund comes from (70%) the European Fund of Regional Development (EFRD) and from (30%) National resources.
Further Information

Publication History

Received: 23 July 2008

Accepted after major revision: 04 March 2008

Publication Date:
23 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Human tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohisto-chemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RTPCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.

Keywords

Cell lines - colorectal cancer - human stratum corneum chymotryptic enzyme - KLK7 - tumor markers
 

  • References

  • 1 American Cancer Society.. Cancer facts and figures, 2005. Atlanta: American Cancer Society; 2005
    Search in Google Scholar
  • 2 McCracken M. et al. Cancer incidence, mortality, and associated risk factors among asian americans of chinese, filipino, vietnamese, korean, and Japanese ethnicities. CA Cancer J Clin 2007; 57: 190-205.
    CrossrefPubMedSearch in Google Scholar
  • 3 Duffy MJ. et al. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer 2003; 39: 718-727.
    CrossrefPubMedSearch in Google Scholar
  • 4 Anwar S. et al. Systematic review of genetic influences on the prognosis of colorectal cancer. Brit J Surg 2004; 91: 1275-1291.
    CrossrefPubMedSearch in Google Scholar
  • 5 Borgono CA, Diamandis EP. The emerging roles of human kallikreins in cancer. Nat Rev Cancer 2004; 4: 876-890.
    CrossrefPubMedSearch in Google Scholar
  • 6 Yousef GM, Diamandis EP. Tissue kallikrein: new players in normal and abnormal cell growth. Thromb Haemost 2003; 90: 7-16.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Hansson L. et al. Cloning, expression and characterization of stratum corneum chymotryptic enzyme. J Biol Chem 1994; 269: 19420-19426.
    PubMedSearch in Google Scholar
  • 8 Yousef GM. et al. The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family; genomic characterization, mapping, tissue expression, and hormonal regulation. Gene 2000; 254: 119-128.
    CrossrefPubMedSearch in Google Scholar
  • 9 Ekholm IE. et al. Stratum corneum tryptic enzyme in normal edidermis: a missing link in the desquamation process. J Invest Dermatol 2000; 114: 56-63.
    CrossrefPubMedSearch in Google Scholar
  • 10 Descargues P. et al. Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrom. J Invest Dermatol 2006; 126: 1622-1632.
    CrossrefPubMedSearch in Google Scholar
  • 11 Caubet C. et al. Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J Invest Dermatol 2004; 122: 1235-1244.
    CrossrefPubMedSearch in Google Scholar
  • 12 Brattsand M. et al. A proteolytic cascade of kallik-reins in the stratum corneum. J Invest Dermatol 2005; 124: 198-203.
    CrossrefPubMedSearch in Google Scholar
  • 13 Talieri M. et al. Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma. Thromb Haemost 2004; 91: 180-186.
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Dong Y. et al. Differential splicing of KLK5 and KLK7 in epithelial Ovarian Cancer produces Novel variants with potential as cancer biomarkers. Clin Cancer Res 2003; 9: 1710-1720.
    PubMedSearch in Google Scholar
  • 15 Shan SJ. et al. Unfavorable prognostic value of human kallikrein 7 quantified by ELISA in ovarian cancer cytosols. Clin Chem 2006; 52: 1879-1886.
    CrossrefPubMedSearch in Google Scholar
  • 16 Holzscheiter L. et al. Quantititative reverse transcription-PCR assay for detection of mRNA encoding full- length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression levels in breast cancer. Clin Chem 2006; 52: 1070-1079.
    CrossrefPubMedSearch in Google Scholar
  • 17 Santin AD. et al. The serine protease stratum corneum chymotryptic enzyme (kallikrein 7) is highly overexpressed in squamous cervical cancer cells. Gynecol Oncol 2004; 94: 283-288.
    CrossrefPubMedSearch in Google Scholar
  • 18 Singh J. et al. Expression of kallikrein-related peptidases (KRP/Hk5, 7 6, 8) in subtypes of human lung carcinoma. International Immunopharmacology 2008; 8: 300-306.
    CrossrefPubMedSearch in Google Scholar
  • 19 Planque Ch. et al. A multiparametric serum kallik-rein panel for diagnosis of non-small cell lung carcinoma. Clin Cancer Res 2008; 14: 1355-1362.
    CrossrefPubMedSearch in Google Scholar
  • 20 Prezas P. et al. Human tissue Kallikreins 7 and 8 gene expression in intracranial tumors: a clinical study in Greece. Biol Chem 2006; 387: 613-618.
    PubMedSearch in Google Scholar
  • 21 Rittenhouse HG. et al. Human Kallikrein 2 (hK2) and prostatic specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci 1998; 35: 275-268.
    CrossrefPubMedSearch in Google Scholar
  • 22 Yousef GM. et al. In-silico analysis of kallikrein gene expression in pancreatic and colon cancers. Anti-cancer Res 2004; 24: 43-51.
    PubMedSearch in Google Scholar
  • 23 Ogawa K. et al. Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. Clin Cancer Res 2005; 11: 2889-2893.
    CrossrefPubMedSearch in Google Scholar
  • 24 Feng B. et al. Clinical significance of human kallik-rein 10 gene expression in colorectal cancer and gastric cancer. J Gastroenterol Hepatol 2006; 21: 1596-1603.
    CrossrefPubMedSearch in Google Scholar
  • 25 Mathioudaki K. et al. Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer. Biol Chem 2004; 385: 779-783.
    PubMedSearch in Google Scholar
  • 26 Mathioudaki K. et al. SR-A1 gene , member of the human pre-mRNA splicing factors and its expression in colon cancer progression. Biol Chem 2004; 385: 785-790.
    PubMedSearch in Google Scholar
  • 27 Talieri M. et al. Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors. Thromb Haemost 2003; 89: 1081-1088.
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Leoutsakou Th. et al. Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer. Biochem Biophys Res Commun 2006; 344: 667-674.
    CrossrefPubMedSearch in Google Scholar
  • 29 Leoutsakou T. et al. Prognostic significance of the expression of SR-A1, encoding a novel SR- related CTD-associated factor, in breast cancer. Biol Chem 2006; 387: 1613-1618.
    PubMedSearch in Google Scholar
  • 30 Talieri M. et al. Cathepsin B and Cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer Lett 2004; 205: 97-106.
    CrossrefPubMedSearch in Google Scholar
  • 31 Dorn J. et al. Primary tumor levels of human tissue kallikreins affect surgical success and survival in ovarian cancer patients. Clin Cancer Res 2007; 13: 1742-1748.
    CrossrefPubMedSearch in Google Scholar
  • 32 Petraki CD. et al. Cellular distribution of human tissue kallikreins: immunohistochemical localization. Biol Chem 2006; 387: 653-663.
    PubMedSearch in Google Scholar
  • 33 Emami N, Diamandis EP. Human tissue kallikreins: A road under construction. Clin Chim Acta 2007; 381: 78-84.
    CrossrefPubMedSearch in Google Scholar
  • 34 Kountourakis P. et al. Expression and prognostic significance of human kallikrein 8 protein levels in advanced ovarian cancer by using automated quantitative analysis. Thromb Haemost 2009; 101: 541-546.
    Thieme ConnectPubMedSearch in Google Scholar
  • 35 Thomadaki H. et al. Treatment of PC3 prostate cancer cells with Mitoxanthrone, Etoposide, Doxorubicin and Carboplatin induces distinct alterations in the expression of kallikreins 5 and 11. Thromb Haemost 2009; 101: 373-380.
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Papachristopoulou G. et al. Expression analysis and study of KLK4 in benign and malignant breast tumours. Thromb Haemost 2009; 101: 381-387.
    Thieme ConnectPubMedSearch in Google Scholar
  • 37 Chung CH. et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell 2004; 5: 489-500.
    CrossrefPubMedSearch in Google Scholar
  • 38 Roman-Gomez J. et al. The normal epithelial cell-specific 1 (NES1) gene, a candidate tumor suppressor gene on chromosome 19q13.3–4, is downregulated by hypermethylation in acute lymphoblastic leukemia. Leukemia 2004; 18: 362-365.
    CrossrefPubMedSearch in Google Scholar
  • 39 Christophi GP. et al. Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease. J. Neurochem 2004; 91: 1439-1449.
    CrossrefPubMedSearch in Google Scholar
  • 40 Pampalakis G. et al. The epigenetic basis for the aberrant expression of kallikreins in human cancers. Biol Chem 2006; 387: 795-799.
    PubMedSearch in Google Scholar
  • 41 Pampalakis G. et al. Cloning and chracterization of novel isoforms of the human kallikrein 6 gene. Biochem Biophys Res Commun 2004; 320: 54-61.
    CrossrefPubMedSearch in Google Scholar
  • 42 Shaw J, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem 2007; 53: 1423-1432.
    CrossrefPubMedSearch in Google Scholar
  • 43 Johnson SK. et al. Kallikrein 7 enhances pancreatic cancer cell invation by shedding E-cadherin. Cancer 2007; 109: 1811-1820.
    CrossrefPubMedSearch in Google Scholar
  • 44 Dong Y. et al. Tissue-specific promoter utilisation of the kallikrein-related peptidase genes, KLK5 and KLK7, and cellular localisation of the encoded proteins suggest roles in exocrine pancreatic function. Biol Chem 2008; 389: 99-109.
    PubMedSearch in Google Scholar
  • 45 Ramani VC, Haun RS. The extracellular matrix protein fibronectin is a substrate for kallikrein 7. Biochem Biophys Res Commun 2008; 369: 1169-1173.
    CrossrefPubMedSearch in Google Scholar
  • 46 Pampalakis G, Sotiropoulou G. Tissue kallikrein proteolytic cascade pathways in normal physiology and cancer. Biochim Biophys Acta 2007; 1776: 22-31.
    PubMedSearch in Google Scholar
  • 47 Paliouras M, Diamandis EP. The kallikrein world: an update on the human tissue kallikreins. Biol Chem 2006; 387: 643-652.
    PubMedSearch in Google Scholar
  • 48 Lundwall A, Brattsand M. Kallikrein-related peptidases. Cell Mol Life Sci 2008; 65: 2019-2038.
    CrossrefPubMedSearch in Google Scholar