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Type: Artigo de periódico
Title: Cathepsin K Is Present in Invasive Oral Tongue Squamous Cell Carcinoma In Vivo and In Vitro
Author: Bitu, CC
Kauppila, JH
Bufalino, A
Nurmenniemi, S
Teppo, S
Keinanen, M
Vilen, ST
Lehenkari, P
Nyberg, P
Coletta, RD
Salo, T
Abstract: Objectives: Cathepsin K, a lysosomal cysteine protease, is expressed in the tumor microenvironment (TME) of skin carcinoma, but nothing is known about cathepsin K in oral tongue squamous cell carcinoma (OTSCC). Our aim was to describe the expression of cathepsin K in invasive OTSCC in vitro and in a series of clinical cancer specimens. Materials and Methods: OTSCC invasion in vitro was studied using invasive HSC-3 tongue carcinoma cells in 3D organotypic models. In total, 121 mobile tongue OTSCCs and 10 lymph node metastases were analyzed for cathepsin K expression. The association between cathepsin K expression and clinicopathological factors was evaluated. Results: Cysteine protease inhibitor E64 and cathepsin K silencing significantly (p < 0.0001) reduced HSC-3 cell invasion in the 3D models. Cathepsin K was expressed in a majority of carcinoma and metastatic cells, but the expression pattern in carcinoma cells did not correlate with clinical parameters. Instead, the weak expression of cathepsin K in the invasive TME front correlated with increased overall recurrence (p < 0.05), and in early-stage tumors this pattern predicted both cancer recurrence and cancer-specific mortality (p < 0.05 and p < 0.005, respectively). Conclusions: Cathepsin K is expressed in OTSCC tissue in both carcinoma and TME cells. Although the diminished activity and expression in aggressive tongue HSC-3 cells reduced 3D invasion in vitro, the amount of cathepsin K in carcinoma cells was not associated with the outcome of cancer patients. Instead, cathepsin K in the invasive TME front seems to have a protective role in the complex progression of tongue cancer.
Country: EUA
Editor: Public Library Science
Citation: Plos One. Public Library Science, v. 8, n. 8, 2013.
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0070925
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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