Stromal expression of cathepsin K in squamous cell carcinoma

Yan, Xiaofeng; Takahara, Masakazu; Xie, Lining; Oda, Yoshinao; Nakahara, Takeshi; Uchi, Hiroshi; Takeuchi, Satoshi; Tu, Yating; Moroi, Yoichi; Furue, Masutaka

doi:10.1111/j.1468-3083.2010.03743.x

Cited by 23 publications

(33 citation statements)

References 16 publications

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“…The human cysteine cathepsin family includes 11 members which share a conserved activated site, and they primarily function as intracellular proteases mediating terminal nonspecific bulk proteolysis in the acidic environment of lysosomes via phagocytosis [18]. CTSK degrades components of the ECM and basement membranes, and is overexpressed in stromal Fbs at the invasive front of various malignant tumors [9][10][11][12][13][14]19,20]. However, the regulatory mechanism and implication of fibroblastic CTSK expression remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…CTSK has a uniquely high potency to degrade a wide range of collagens at multiple sites within the triple helix as well as at extra-helical regions [8]. Previous reports have shown that CTSK expression is implicated in the invasive growth of primary tumors in prostate, breast, thyroid and cutaneous squamous cell carcinoma (SCC), where CTSK overexpression by stromal Fbs is associated with an increased invasive potential [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Xie¹,

Moroi²,

Hayashida³

et al. 2011

Journal of Dermatological Science

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Xie¹,

Moroi²,

Hayashida³

et al. 2011

Journal of Dermatological Science

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“…Strong cathepsin K expression was also observed in primary melanomas and melanoma metastases (Quintanilla -Dieck et al, 2008 ). In squamous cell carcinoma, expression of cathepsin K by stromal fibroblasts was stimulated by the tumor cells via secretion of interleukin-1 α and correlated with the invasiveness of the tumor Yan et al , 2011 ).…”

Section: Cathepsin K In Cancermentioning

confidence: 94%

Cathepsin K: a unique collagenolytic cysteine peptidase

Novinec

Lenarčič²

2013

Biological Chemistry

119

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Cathepsin K has emerged as a promising target for the treatment of osteoporosis in recent years. Initially identified as a papain-like cysteine peptidase expressed in high levels in osteoclasts, the important role of this enzyme in bone metabolism was highlighted by the finding that mutations in the CTSK gene cause the rare recessive disorder pycnodysostosis, which is characterized by severe bone anomalies. At the molecular level, the physiological role of cathepsin K is reflected by its unique cleavage pattern of type I collagen molecules, which is fundamentally different from that of other endogenous collagenases. Several cathepsin K inhibitors have been developed to reduce the excessive bone matrix degradation associated with osteoporosis, with the frontrunner odanacatib about to successfully conclude Phase 3 clinical trials. Apart from osteoclasts, cathepsin K is expressed in different cell types throughout the body and is involved in processes of adipogenesis, thyroxine liberation and peptide hormone regulation. Elevated activity of cathepsin K has been associated with arthritis, atherosclerosis, obesity, schizophrenia, and tumor metastasis. Accordingly, its activity is tightly regulated via multiple mechanisms, including competitive inhibition by endogenous macromolecular inhibitors and allosteric regulation by glycosaminoglycans. This review provides a state-of-the-art description of the activity of cathepsin K at the molecular level, its biological functions and the mechanisms involved in its regulation.

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“…It has an important role in many other tissues, as well [13], [14], [18], [19]. In general, the expression of cathepsin K in normal tissue seems to be associated with the process of extracellular matrix turnover.…”

Section: Introductionmentioning

confidence: 99%

Cathepsin K Is Present in Invasive Oral Tongue Squamous Cell Carcinoma In Vivo and In Vitro

et al. 2013

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ObjectivesCathepsin 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 MethodsOTSCC 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.ResultsCysteine 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).ConclusionsCathepsin 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.

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Stromal expression of cathepsin K in squamous cell carcinoma

Cited by 23 publications

References 16 publications

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Cathepsin K: a unique collagenolytic cysteine peptidase

Cathepsin K Is Present in Invasive Oral Tongue Squamous Cell Carcinoma In Vivo and In Vitro

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