SEPRASE, A MEMBRANE-BOUND PROTEASE, IS OVEREXPRESSED BY INVASIVE DUCTAL CARCINOMA-CELLS OF HUMAN BREAST CANCERS

The increased cell surface expression of the serine integral membrane protease, seprase, has been associated with the invasive behavior of h uman melanoma cell lines in vitro. The present study investigates the expression of seprase in malignant, premalignant, benign, and normal h uman breast tissues, The 170-kDa gelatinase activity of seprase was id entified in extracts of infiltrating ductal carcinomas (IDC). Protein bands corresponding to the proteolytically active 170-kDa seprase dime r and its 97-kDa seprase subunit protein were identified by immunoblot analysis of IDC extracts using an anti-serum elicited against immunoa ffinity-purified seprase. Immunohistochemical analysis of seprase expr ession in 41 formalin-fixed and paraffin-embedded specimens of human b reast 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 th e lymphoid tissue in affected nodes was not stained. Neoplastic cells in DC irt situ (5 cases) exhibited variable levels of staining. Epithe lial cells of benign fibroadenoma specimens (2 cases) and benign proli ferative breast disease (5 cases) exhibited little or no immunoreactiv ity. Epithelial cells of normal breast tissue (1 case) were not staine d. The overexpression of seprase by DC cells is consistent with sepras e having a role in facilitating invasion and metastasis of IDC of the breast. The cell surface localization of seprase could be used to targ et therapeutic agents to malignant breast cells.