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Clinical significance of kallikrein-related peptidase-4 in oral cancer.
Anticancer Res 2015; 35(4):1861-6AR

Abstract

Kallikrein-related-peptidase-4 (KLK4), a serine protease originally discovered in developing tooth with broad target sequence specificity, serves vital functions in dental enamel formation. KLK4 is involved in degradation of extracellular matrix proteins and it is thought that this proteolytic activity could also promote tumor invasion and metastasis. Recent studies have associated KLK4 expression with tumor progression and clinical outcome, particularly in prostate and ovarian cancer. Very little is known in regard KLK4 involvement in oral squamous cell carcinomas (OSCCs). Our objective was to investigate KLK4 expression in OSCC pathogenesis and disease progression. KLK4 expression was evaluated by immunohistochemistry, western blots and zymograms in OSCC lines. Invasion assays using high versus low/undetectable KLK4-expressing OSCC cell lines were performed jointly with KLK4 siRNA inhibition. A large collection of OSCC specimens was evaluated for KLK4 expression and correlation with patients' characteristics and outcomes were determined. Our data indicate that KLK4 is differentially expressed in oral carcinomas. OSCC cell lines with high invasive and metastatic potential have the highest levels of KLK4 expression. KLK4 mRNA and protein expression correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines. Consistently, KLK4 expression is stronger in primary tumors that later either recurred or developed metastases, suggesting that its preferential expression in OSCC might contribute to individual tumor biology. Therefore, this study provides supportive evidence in favor of a prognostic value for KLK4 in OSCC and suggests that KLK4 could serve as a potential therapeutic target in patients with oral cancer.

Authors+Show Affiliations

Department of Pediatric Dentistry and Orthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. Department of Computational Medicine and Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI, U.S.A.Department of Clinical and Experimental Medicine, Section of Anatomic Pathology, University of Foggia, Foggia, Italy.Department of Pediatric Dentistry and Orthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. Department of Otolaryngology-Head & Neck Surgery, Medical School, University of Michigan, Ann Arbor, MI, U.S.A.Department of Pediatric Dentistry and Orthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. Department of Otolaryngology-Head & Neck Surgery, Medical School, University of Michigan, Ann Arbor, MI, U.S.A.Department of Biomaterials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A.Department of Pathology, School of Medicine, University of Texas Health Science Center, San Antonio, TX, U.S.A.Department of Otolaryngology-Head & Neck Surgery, Medical School, University of Michigan, Ann Arbor, MI, U.S.A.Department of Pediatric Dentistry and Orthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A. Department of Otolaryngology-Head & Neck Surgery, Medical School, University of Michigan, Ann Arbor, MI, U.S.A.Department of Otolaryngology-Head & Neck Surgery, Medical School, University of Michigan, Ann Arbor, MI, U.S.A. silvanap@umich.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25862839

Citation

Papagerakis, Petros, et al. "Clinical Significance of Kallikrein-related Peptidase-4 in Oral Cancer." Anticancer Research, vol. 35, no. 4, 2015, pp. 1861-6.
Papagerakis P, Pannone G, Zheng LI, et al. Clinical significance of kallikrein-related peptidase-4 in oral cancer. Anticancer Res. 2015;35(4):1861-6.
Papagerakis, P., Pannone, G., Zheng, L. I., Athanassiou-Papaefthymiou, M., Yamakoshi, Y., McGuff, H. S., ... Papagerakis, S. (2015). Clinical significance of kallikrein-related peptidase-4 in oral cancer. Anticancer Research, 35(4), pp. 1861-6.
Papagerakis P, et al. Clinical Significance of Kallikrein-related Peptidase-4 in Oral Cancer. Anticancer Res. 2015;35(4):1861-6. PubMed PMID: 25862839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical significance of kallikrein-related peptidase-4 in oral cancer. AU - Papagerakis,Petros, AU - Pannone,Giuseppe, AU - Zheng,L I, AU - Athanassiou-Papaefthymiou,Maria, AU - Yamakoshi,Yashuo, AU - McGuff,Howard Stan, AU - Shkeir,Omar, AU - Ghirtis,Konstantinos, AU - Papagerakis,Silvana, PY - 2015/4/12/entrez PY - 2015/4/12/pubmed PY - 2015/10/1/medline KW - Kallikrein-related-peptidase-4 (KLK4) KW - Oral squamous cell carcinoma (OSCC) KW - cell lines KW - clinical outcome KW - invasion KW - metastasis SP - 1861 EP - 6 JF - Anticancer research JO - Anticancer Res. VL - 35 IS - 4 N2 - Kallikrein-related-peptidase-4 (KLK4), a serine protease originally discovered in developing tooth with broad target sequence specificity, serves vital functions in dental enamel formation. KLK4 is involved in degradation of extracellular matrix proteins and it is thought that this proteolytic activity could also promote tumor invasion and metastasis. Recent studies have associated KLK4 expression with tumor progression and clinical outcome, particularly in prostate and ovarian cancer. Very little is known in regard KLK4 involvement in oral squamous cell carcinomas (OSCCs). Our objective was to investigate KLK4 expression in OSCC pathogenesis and disease progression. KLK4 expression was evaluated by immunohistochemistry, western blots and zymograms in OSCC lines. Invasion assays using high versus low/undetectable KLK4-expressing OSCC cell lines were performed jointly with KLK4 siRNA inhibition. A large collection of OSCC specimens was evaluated for KLK4 expression and correlation with patients' characteristics and outcomes were determined. Our data indicate that KLK4 is differentially expressed in oral carcinomas. OSCC cell lines with high invasive and metastatic potential have the highest levels of KLK4 expression. KLK4 mRNA and protein expression correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines. Consistently, KLK4 expression is stronger in primary tumors that later either recurred or developed metastases, suggesting that its preferential expression in OSCC might contribute to individual tumor biology. Therefore, this study provides supportive evidence in favor of a prognostic value for KLK4 in OSCC and suggests that KLK4 could serve as a potential therapeutic target in patients with oral cancer. SN - 1791-7530 UR - https://www.unboundmedicine.com/medline/citation/25862839/Clinical_significance_of_kallikrein_related_peptidase_4_in_oral_cancer_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=25862839 DB - PRIME DP - Unbound Medicine ER -