Aminopeptidase activities in breast cancer tissue.

BACKGROUND Endopeptidases such as cathepsins help determine the prognosis of breast cancer (BC). However, little information is available about the role in BC of aminopeptidases (APs), which have been implicated in the metabolism of several local hormonal factors. METHODS Using aminoacyl-beta-naphthylamides as substrates, we measured fluorometrically alanyl-AP, arginyl-AP, cystinyl-AP, glutamyl-AP, aspartyl-AP, and pyroglutamyl-AP activities in their soluble and membrane-bound forms in surgically removed BC tissue from which we separated samples of neoplastic, adjacent tumoral, and unaffected surrounding tissue. RESULTS Compared with unaffected tissue, neoplastic tissue had significantly higher activities of soluble alanyl-AP (553.9 +/- 82.8 vs 1615.2 +/- 183.0 pmol/mg protein; P <0.001), arginyl-AP (372.4 +/- 56.6 vs 1027.2 +/- 143.5 pmol/mg protein; P <0.001), and cystinyl-AP (74.8 +/- 10.0 vs 282.9 +/- 37.2 pmol/mg protein; P <0.001), and of membrane-bound arginyl-AP (457.7 +/- 97.9 vs 886.6 +/- 140.0 pmol/mg protein; P <0.01). However, membrane-bound aspartyl-AP activity was significantly lower in neoplastic tissue (17.3 +/- 1.4 vs 9.2 +/- 1.2 pmol/mg protein; P <0.05) and pyroglutamyl-AP activity was significantly lower in neoplastic and adjacent tissues (12.8 +/- 0.9 vs 7.0 +/- 1. 2 and 8.0 +/- 1.3 pmol/mg protein; P <0.001 for both comparisons). CONCLUSIONS The present results document changes in AP activities in BC tissue. These changes may reflect the functional status of the AP substrates, which can be selectively activated or inhibited locally in the affected tissue as a result of specific conditions brought about by the tumor.

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