Cathepsin K is present in invasive oral tongue squamous cell carcinoma in vivo and in vitro.
OBJECTIVE
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.


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.
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.
Carolina C
CC
Bitu
Joonas H
JH
Kauppila
Andréia
A
Bufalino
Sini
S
Nurmenniemi
Susanna
S
Teppo
Meeri
M
Keinänen
Suvi-Tuuli
ST
Vilen
Petri
P
Lehenkari
Pia
P
Nyberg
Ricardo D
RD
Coletta
Tuula
T
Salo
D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009924:Organ Culture Techniques; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics
D015853:Cysteine Proteinase Inhibitors; D056657:Cathepsin K; D007930:Leucine; C108192:aloxistatin