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

Xie, Lining; Moroi, Yoichi; Hayashida, Shinsaku; Tsuji, Gaku; Takeuchi, Satoshi; Shan, Baoen; Nakahara, Takeshi; Uchi, Hiroshi; Takahara, Masakazu; Furue, Masutaka

doi:10.1016/j.jdermsci.2010.09.005

Cited by 20 publications

(21 citation statements)

References 21 publications

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“…In addition to that, the CTKS gene expression was up-regulated in co-cultured A431-SCCs. CTKS encodes for cathepsin K, a cysteine protease with strong collagenolytic and elastolytic properties which is involved in extracellular matrix turnover [43,44]. CTKS up-regulation has been associated with tumor progression in squamous cell carcinomas of the skin [43].…”

Section: Discussionmentioning

confidence: 99%

Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications

et al. 2014

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IntroductionThis is the first study evaluating the interactions of human adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells (SCCs), with regard to a prospective cell-based skin regenerative therapy and a thereby unintended co-localization of ADSCs and SCCs.MethodsADSCs were co-cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell-cell interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPS). Results of co-culture were compared to those of the respective mono-culture.ResultsADSCs’ proliferation on the plate was significantly increased when co-cultured with A431-SCCs (P = 0.038). PSCCs and ADSCs significantly decreased their proliferation in co-culture if cultured on the plate (P <0.001 and P = 0.03). The migration of pSCC was significantly increased in co-culture (P = 0.009), as well as that of ADSCs in A431-SCC-co-culture (P = 0.012). The invasive behavior of pSCCs and A431-SCCs was significantly increased in co-culture by a mean of 33% and 35%, respectively (P = 0.038 and P <0.001). Furthermore, conditioned media from co-cultured ADSC-A431-SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay in vitro.In A431-SCC-co-culture 36 genes were up- and 6 were down-regulated in ADSCs, in A431-SCCs 14 genes were up- and 8 genes were down-regulated. In pSCCs-co-culture 36 genes were up-regulated in ADSCs, two were down-regulated, one gene was up-regulated in pSCC, and three genes were down-regulated. Protein expression analysis revealed that three proteins were exclusively produced in co-culture (CXCL9, IL-1b, and MMP-7). In A431-SCC-co-culture the concentration of 17 proteins was significantly increased compared to the ADSCs mono-culture (2.8- to 357-fold), and 15 proteins were expressed more highly (2.8- to 1,527-fold) compared to the A431-SCCs mono-culture. In pSCC-co-culture the concentration of 10 proteins was increased compared to ADSCs-mono-culture (2.5- to 77-fold) and that of 15 proteins was increased compared to pSCC mono-culture (2.6- to 480-fold).ConclusionsThis is the first study evaluating the possible interactions of primary human ADSCs with human SCCs, pointing towards a doubtlessly increased oncological risk, which should not be neglected when considering a clinical use of isolated human ADSCs in skin regenerative therapies.

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Section: Discussionmentioning

confidence: 99%

Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications

et al. 2014

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“…Either both cell types can be introduced into the upper well of the migration chamber or one can be placed in the lower well and the other cell type in the upper well depending on the question to be addressed. For example, the role and source of cathepsin K in squamous cell carcinoma invasion was studied by coculturing a squamous cell carcinoma line, A431, with fibroblasts together in 3D culture on BME/Matrigel in the upper well of the invasion chamber [70]. When cocultured, the squamous cells were significantly more invasive than when the fibroblasts were not present.…”

Section: Invasion Assay -Boyden Chambermentioning

confidence: 99%

Matrigel: From discovery and ECM mimicry to assays and models for cancer research

Benton

Arnaoutova

George

et al. 2014

Advanced Drug Delivery Reviews

377

303

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“…Such tasks may be brought about directly by processing of ECM constituents and indirectly by initiating proteolytic cascades in cancer invasion and metastasis [28,29,32,39,54,74]. Undoubtedly, cathepsin K is one of the cysteine peptidases with such functions in cancer [54,[74][75][76][77]. However, ECM degradation besides type I collagen processing in bone turnover has also been shown to occur in physiology for tissue remodelling during wound healing of the skin or the gastro-intestinal tract and to be mediated by a number of different cysteine cathepsins, namely cathepsins B, D and L [22,29,32,78].…”

Section: Bone As a Th Target Tissuementioning

confidence: 99%

Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease

Dauth

Arampatzidou

Rehders

et al. 2011

Clinic Rev Bone Miner Metab

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The human genome encodes 11 cysteine cathepsins belonging to the papain-like family of cysteine peptidases that are known predominantly as endo-lysosomal enzymes. However, it is now understood that the functions and activities of cysteine cathepsins are not limited to endo-lysosomal compartments, as they are also active in the peri-and extracellular space. The thyroid gland is an endocrine organ where such intra-and extracellular proteolytic activities are required to solubilize the prohormone thyroglobulin from its luminal, covalently cross-linked storage forms for subsequent processing into smaller protein fragments and thyroid hormone liberation. Cathepsin K has been identified as one of the cysteine cathepsins with a crucial role in thyroglobulin processing. However, cathepsin K has mainly been a key focus of attention in the last few years because of its high expression in osteoclasts and due to its essential role as collagenase and elastase important for bone remodelling. Besides its remarkable function as an endopeptidase acting on highmolecular mass, covalently cross-linked extracellular substrates such as type I collagen, elastin or thyroglobulin, cathepsin K is also one of the very few proteolytic enzymes that is able to directly liberate thyroxine from thyroglobulin fragments by exopeptidase action. Thus, thyroid cathepsin K is now accepted as a cysteine peptidase with a vital role in liberation of thyroid hormones, which in turn are essential for homoeostasis by triggering a number of important biological processes, ranging from growth and brain development in young vertebrates to tissue remodelling events during morphogenesis or wound healing, as well as control of metabolic pathways and thermoregulation in adults. This review focuses on thyroid cathepsin K and will discuss how localization and trafficking within thyroid epithelial cells explain its thyroid-specific functions. The effects of targeted cathepsin K gene ablation will be summarized from the perspective of the thyroid gland, and we will propose potential consequences of short-and long-term inhibition of thyroid cathepsin K activity for the main thyroid hormone target tissues, namely bone, cardiovascular and immune systems, intestine, and the central nervous system, in addition to the thyroid gland itself.

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

Abstract: The CTSK-upregulated Fbs generated by SCC-derived IL-1α may play a crucial role in the progression and invasion of SCC.

Cited by 20 publications

References 21 publications

Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications

Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications

Matrigel: From discovery and ECM mimicry to assays and models for cancer research

Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease

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