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obstructive pulmonary disease (COPD) (Zheng et al. 2000 ). Inhibition of these
enzymes was found to decrease the emphysema and inflammation. Increased
cathepsin L activity found in alveolar macrophage and bronchoalveolar lavage
fluid has also been linked with promoting emphysema (Takahashi et al. 1993 ). In
other inflammatory conditions such as silicosis and sarcoidosis, mature active
cathepsins (B, H, K, L, and S) have been found in the bronchoalveolar fluid
suggesting that they play a role in ECM degradation and therefore disease patho-
genesis (Perdereau et al. 2006 ; Serveau-Avesque et al. 2006 ).
2.5.4 Skin (Collagenolytic and Elastolytic Cathepsins)
Cathepsins were not found to have high expression in normal skin fibroblasts
although their expression was found to be much higher in scars (Runger et al.
2007 ). Wound healing and scar formation requires a tightly controlled equilibrium
between synthesis and degradation of ECM proteins. After the completion of
wound healing, an antifibrotic state is needed to return the scar to a normal state.
Cathepsin K has been suggested to be important during this antifibrotic activity due
to its high expression in the dermal fibroblasts of scars and high collagenolytic and
elastolytic activities (Runger et al. 2007 ). Cathepsin K was found in fibroblast
lysosomes and is thought to act in the endocytic degradation pathway rather than in
the extracellular pathway. Collagens I and IV were found to be internalized into
lysosomes for internal degradation (Quintanilla-Dieck et al. 2008 ).
2.5.5 Cancer
Cancer progression is characterized by the degradation of the ECM with MMPs,
cysteine, and serine proteases. Many cathepsins have now been suggested to play a
role in tumor progression, including cathepsins B, L, H, X, S, and K contributing to
invasion/metastasis and angiogenesis; however, most work has focused on cathe-
psins B and L (Coulibaly et al. 1999 ; Mohamed and Sloane 2006 ; Roshy et al.
2003 ). Cathepsins have been described to have an increased expression and activity
in tumor cells and being involved in cancer cell invasion and migration through
ECM components in a variety of cancer types. Cathepsins B and L have been shown
to degrade collagen IV, fibronectin, and laminin components of the basement
membrane (Buck et al. 1992 ; Ishidoh and Kominami 1995 ; Lah et al. 1989 ). Several
in vitro experiments have shown the inhibition of specific cysteine cathepsins to
decrease the invasion of tumor cells through matrigel or ECM in a range of cancers,
including melanoma, glioblastoma, colon, prostate, and lung cancers (Coulibaly
et al. 1999 ; Levicar et al. 2002 ). Studies have shown that both intracellular and
extracellular inhibitions of cathepsins can inhibit invasion, suggesting that both the
secretion of active enzyme and intracellular degradation pathways are important. In
prostate, colon, and breast cancer cells, intracellular type IV collagen degradation
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