Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using confocal fluorescence microscopy with a monoclonal antibody, we have localized the receptor for urokinase plasminogen activator (uPAR) in MDA-MB-231 human breast cancer cells migrating into a reconstituted basement membrane. Patchy and polarized uPAR immunoreactivity was found at the cell membrane, and strong staining was found both in the ruffled border or leading edge of the cells and at pseudopodia penetrating into the membrane. Intracellular uPAR staining was localized in the paranuclear region and in rounded granule-like structures; some of these were identified as lysosomes by double staining for uPAR and the lysosomal enzyme cathepsin D. Urokinase plasminogen activator (uPA) activity has previously been shown to play a role in migration of cells into basement membranes, and it has been proposed that uPAR also is involved in this process. uPA is known to be internalized and degraded after complex formation with the inhibitor PAI-1. Lysosomal uPAR immunoreactivity may result from concomitant internalization of the receptor.
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PMID:Confocal fluorescence microscopy of urokinase plasminogen activator receptor and cathepsin D in human MDA-MB-231 breast cancer cells migrating in reconstituted basement membrane. 751 99

Urokinase plasminogen activator (uPA) is a multifunctional protein involved in both extracellular proteolysis and signal transduction. uPA usually mediates its actions while attached to a membrane-bound receptor, termed uPAR. In this study, uPA and its receptor were measured at both protein and mRNA levels in breast cancer. At both levels, concentrations of uPA were significantly correlated with those for uPAR. uPA levels also correlated significantly with cathepsin B and cathepsin D but not with cathepsin L, MMP-8 or MMP-9 levels. Irrespective of the cut-off point used (e.g., median, tertile or quartile values), uPA was a significant prognostic marker for breast cancer.
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PMID:Urokinase plasminogen activator as a predictor of aggressive disease in breast cancer. 879 99

We compared macrophage density, assessed by enumeration of peritumoral mononuclear cell immunoreactivity for HAM 56, to clinicopathologic features and to immunostaining for two "invasion-associated" proteases (Cathepsin D and Urokinase plasminogen activator) in 80 breast carcinomas. Diffuse (2+) infiltrates of HAM 56- positive mononuclear cells were present in 27 cases (34%) and 43 (54%) exhibited focal (1+) infiltrates. Presence of 2+ macrophage infiltrates correlated significantly with poor differentiation. None of the seven well-differentiated cases exhibited 2+ infiltrates, whereas 9/43 (21%) moderately differentiated and 18/30 (60%) poorly differentiated tumors were diffusely infiltrated (p = .001). Wide-spread macrophage infiltrates were also more frequent in cases with advanced stage (23% of node negative vs 40% of node positive cases, p = NS). Forty-four percent of the cases with diffuse macrophage infiltrates were cathepsin D positive (i.e. in host derived cells) vs only 18% with focal macrophage infiltrates (p = .002). A similar relationship was observed between staining for HAM 56 and urokinase-type plasminogen activator (p = .02). Disease recurrences (50 months median follow-up) were more frequent in patients with 2+ (17/27, 63%) as opposed to 0+ (1/10, 10%) macrophage infiltrates (p = .01). We conclude that the density of stromal macrophage infiltrates is associated with clinical aggressiveness in breast carcinomas. Further, this relationship may reflect contribution of host derived macrophages to invasion and metastasis through elaboration of proteases which putatively mediate degradation and remodeling of extracellular matrix.
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PMID:Clinicopathologic analysis of macrophage infiltrates in breast carcinoma. 882 15