Cathepsin B: a potential prognostic marker for inflammatory breast cancer

Abstract

BackgroundInflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.MethodsIn this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups.ResultsOur results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC.ConclusionsCTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC.

Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression

“…Several steps to invasive tumor growth are facilitated by proteolysis (1). Among other protease families lysosomal cysteine cathepsins, especially cathepsin B and L, are often found to be highly expressed in aggressive tumors (2)(3)(4).…”

V-ATPase inhibition by archazolid leads to lysosomal dysfunction resulting in impaired cathepsin B activationin vivo

“…22,23 Nevertheless, cathepsin B expression is increased in different types of cancer like prostate cancer, oesophageal adenocarcinoma, breast cancer or colorectal cancer. [24][25][26][27][28][29][30] Cathepsin B (CTSB) is synthesized at the rough endoplasmic reticulum as preprocathepsin B. Signal peptides target preproCTSB to the ER lumen, where it becomes cleaved to proCTSB.…”

Inflammatory Breast Neoplasms: A Systematic Review

“…Several studies investigated diagnosis and treatment 4,10,[12][13][14][15][16][17][18][19]21,23,26,28 , two of which 10,15 show that MRI (Magnetic Resonance Imaging) is significantly more accuracy for diagnosing IBC. LePetross 9 argues that MRI has a 98% accuracy rate in targeting IBC when compared with ultrasonic imaging (94%) and a mammogram (65%).…”

“…IBC tends to develop at a younger age than the more common form of breast cancer 5 . Distinct signs and symptoms develop quickly and include redness, thickening (edema/swelling) and ridging or orange-peel like textureof the skin -peaud'orange 4 in French.…”

“…Rapid blood and lymphatic spread and breast tumor emboli are the main features ofIBC 4 . With an average survival rate of three years, IBC accounts for about 2.5% of all breast cancer types in the US.…”