Cathepsin B and D expression in squamous cell carcinoma

Abstract

To elucidate involvement of proteinases in malignancy of keratinocytes, expression of cathepsin B, a cysteine proteinase, and cathepsin D, an aspartic proteinase, was ascertained in formalin-fixed paraffin-embedded specimens of normal skin, squamous cell carcinoma (SCC). Bowen's disease, seborrhoeic keratosis and basal cell carcinoma (BCC). Presence of procathepsin B and an intermediate form of cathepsin D was confirmed by Western blotting and enzyme activity analysis. Cathepsin B stained more intensely in SCC tumour cells than in normal epidermis; staining patterns were diffuse, granular or both. Diffuse and granular patterns (procathepsin B and mature enzyme, respectively) appeared in inner and outer parts of tumour islands, respectively. Five of 20 cases of Bowen's disease showed diffuse enhanced cathepsin B expression; 20 cases of seborrhoeic keratosis or BCC did not. Cathepsin D stained intensely in tumour cells of half the SCC cases. The staining manner and distribution of cathepsins B and D was similar in the cytoplasm of cancer cells. No enhanced staining of cathepsin D was seen in any cases of Bowen's disease, seborrhoeic keratosis, or BCC. Coexistence and localization of active mature forms of cathepsins B and D suggests that cooperation between the two enzymes may play an important part in invasion of SCC.

Optical Imaging of Cancer-Related Proteases Using Near-Infrared Fluorescence Matrix Metalloproteinase-Sensitive and Cathepsin B-Sensitive Probes

“…This lysosomal cysteine protease is overexpressed in cancer cells, such as gastric or colon cancers 24, 25. Squamous cell carcinoma cells (SCC-7) was also confirmed that it express high levels of cathepsin B 26, 27. Because overexpressed MMPs and cathepsin B play important biological functions in tumor, many imaging probes targeting these proteases have been developed for cancer diagnosis 28, 29.…”

Immunohistochemical expression of cathepsin D and matrix metalloproteinase-9 in common epidermal tumors

“…Kawada et al [21] noted that half of SCC cases showed enhanced cathepsin D expression, but Bowen's disease, SK, or BCC did not show any staining for cathepsin D. They concluded that upward production of cathepsin D might be associated with malignancy of keratinocytes. It has also been suggested that the catalytic activity of secreted cathepsin D may be implicated in releasing growth factors, such as fibroblast growth factor-2, from the ECM [22].…”

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

“…However, we emphasize that our observations should be evaluated in a larger series of prostate samples before a definitive conclusion can be reached. Previously, Kawada et al (1996) observed diffuse immunostaining for proenzyme and granular staining for mature CB in squamous cell cancer and suggested that there may be some differences in subcellular localization of these two forms of CB. Distribution of mature CB has been reported in several malignant tumors of solid organs (see Campo et al, 1994;Sloane et al, 1994a,b;Elliott and Sloane, 1996).…”