The increased cell surface expression of the
serine integral membrane
protease,
seprase, has been associated with the invasive behavior of human
melanoma cell lines in vitro. The present study investigates the expression of
seprase in malignant, premalignant, benign, and normal human breast tissues. The 170-kDa
gelatinase activity of
seprase was identified in extracts of infiltrating
ductal carcinomas (IDC).
Protein bands corresponding to the proteolytically active 170-kDa
seprase dimer and its 97-kDa
seprase subunit protein were identified by immunoblot analysis of IDC extracts using an antiserum elicited against immunoaffinity-purified
seprase. Immunohistochemical analysis of
seprase expression in 41
formalin-fixed and
paraffin-embedded specimens of human breast tissue revealed preferential immunoreactivity with the malignant cells of IDC (27 cases). Within individual IDC specimens, the stromal cells or morphologically normal epithelium revealed low labeling that was always significantly less than the labeling of neoplastic cells.
Lymph node metastases of IDC cells were also strongly positive, but the lymphoid tissue in affected nodes was not stained. Neoplastic cells in DC in situ (5 cases) exhibited variable levels of staining. Epithelial cells of benign
fibroadenoma specimens (2 cases) and benign proliferative
breast disease (5 cases) exhibited little or no immunoreactivity. Epithelial cells of normal breast tissue (1 case) were not stained. The overexpression of
seprase by DC cells is consistent with
seprase having a role in facilitating invasion and
metastasis of IDC of the breast. The cell surface localization of
seprase could be used to target therapeutic agents to malignant breast cells.