Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-8-12
pubmed:abstractText
Cathepsin K (catK) is a lysosomal cysteine protease with strong collagenolytic activity that mediates bone resorption in osteoclasts. Recently, catK expression has been reported in skin and lung fibroblasts, which suggests a role in maintaining homeostasis of the extracellular matrix outside of bone. Matrix degradation is a pivotal step in tumor invasion and metastasis. As other proteases, in particular matrix metalloproteinases and some cathepsins, but not catK, have been described to mediate melanoma invasion, we studied catK in melanoma. Immunostaining revealed strong catK expression in most primary melanomas and all cutaneous melanoma metastases. Melanocytic nevi also demonstrated catK expression, but it was less intense than in melanomas. Melanoma lines express both the pro- and the active form of catK and internalize extracellular collagen into lysosomes. Inhibition of catK greatly reduced melanoma cell invasion through Matrigel basement membrane matrix and increased detection of internalized collagen. We suggest that catK may play an important role in melanoma invasion and metastasis by mediating intracellular degradation of matrix proteins after phagocytosis. Clinical use of catK inhibitors, a class of medication currently in clinical trials for the treatment of osteoporosis, may be a promising avenue for the treatment of melanoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2281-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18368130-Carcinoma, Basal Cell, pubmed-meshheading:18368130-Carcinoma, Squamous Cell, pubmed-meshheading:18368130-Cathepsin K, pubmed-meshheading:18368130-Cathepsins, pubmed-meshheading:18368130-Cells, Cultured, pubmed-meshheading:18368130-Collagen Type IV, pubmed-meshheading:18368130-Extracellular Matrix, pubmed-meshheading:18368130-Humans, pubmed-meshheading:18368130-Male, pubmed-meshheading:18368130-Melanocytes, pubmed-meshheading:18368130-Melanoma, pubmed-meshheading:18368130-Neoplasm Invasiveness, pubmed-meshheading:18368130-Nevus, Pigmented, pubmed-meshheading:18368130-Phagocytosis, pubmed-meshheading:18368130-RANK Ligand, pubmed-meshheading:18368130-Receptor Activator of Nuclear Factor-kappa B, pubmed-meshheading:18368130-Signal Transduction, pubmed-meshheading:18368130-Skin Neoplasms
pubmed:year
2008
pubmed:articleTitle
Cathepsin K in melanoma invasion.
pubmed:affiliation
Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
pubmed:publicationType
Journal Article