Cathepsin B: a potential prognostic marker for inflammatory breast cancer

Abstract

Background: Inflammatory 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.

Methods: In 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.

Results: Our 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.

Conclusions: CTSB 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.

Figure 1

Photograph of IBC patient showing clinical criteria for IBC diagnosis, i.e., edema, erythema (blue arrow) and peau d'orange (black arrow).

Figure 2

CTSB expression in IBC versus non-IBC tissues. [A] Expression of CTSB in IBC tissue homogenates from 7 different patients (lanes 1-7) was determined by immunoblotting. The forms of CTSB detected were the proenzyme (46 kDa), an intermediate form (38 kDa), single chain mature enzyme (31 kDa) and the heavy chain of double chain mature enzyme (25/26 kDa). β-actin was used as a loading control. [B] Tumor lymphatic emboli in IBC tissue sections, showing CTSB immunostaining (magnification X400). [C] Expression of CTSB in non-IBC tissue homogenates from 7 different patients (lanes 1-7) by immunoblotting analysis. [D] Immunostaining for CTSB in non-IBC tissue (magnification X400).

Figure 3

Cav-1 expression in IBC versus non-IBC tissues. [A] Immunoblot analysis showing expression of cav-1 (22 kDa) in IBC tissue homogenates from 7 different patients (lanes 1-7). [B] Tumor lymphatic emboli in IBC tissue sections showing expression of cav-1 (magnification X400) [C] Cav-1 level of expression in non-IBC tissue homogenates from 7 different patients (lanes 1-7). [D] Non-IBC invasive ductal carcinoma showing expression of cav-1 in breast carcinoma cells (magnification X200).