Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells.

The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically recognized uPARAP in Western blotting and gave a strong signal in immunohistochemistry. The immunohistochemic localization pattern was found to be identical to that of uPARAP mRNA as determined in parallel by in situ hybridization. uPARAP expression was then studied in both benign and malignant breast lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor-associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling.

Schnack Nielsen B ，Rank F ，Engelholm LH ，Holm A ，Danø K ，Behrendt N ... -  《INTERNATIONAL JOURNAL OF CANCER》

Stromal cells associated with early invasive foci in human mammary ductal carcinoma in situ coexpress urokinase and urokinase receptor.

Nielsen BS ，Rank F ，Illemann M ，Lund LR ，Danø K ... -  《INTERNATIONAL JOURNAL OF CANCER》

The urokinase-system in tumor tissue stroma of the breast and breast cancer cell invasion.

Hildenbrand R ，Schaaf A 《INTERNATIONAL JOURNAL OF ONCOLOGY》

Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases.

Fisher JL ，Field CL ，Zhou H ，Harris TL ，Henderson MA ，Choong PF ... -  《-》

Combined overexpression of urokinase, urokinase receptor, and plasminogen activator inhibitor-1 is associated with breast cancer progression: an immunohistochemical comparison of normal, benign, and malignant breast tissues.

Costantini V ，Sidoni A ，Deveglia R ，Cazzato OA ，Bellezza G ，Ferri I ，Bucciarelli E ，Nenci GG ... -  《-》