A Study of Aminopeptidase Activity in the Stroma of Neoplastic Tissue, With a Comparison of Histochemical Techniques2

Abstract

A histochemical examination of aminopeptidase activity in over 120 benign and malignant tumors revealed intense peptidase activity in the stroma adjacent only to those tumors showing invasive characteristics. The method also demonstrated that certain human tumors, such as carcinoma of the stomach, colon, and breast, and a meningioma had aminopeptidase activity within the tumor cells proper. Aminopeptidase activity in the stroma adjacent to invasive tumor is evidence of proteolysis and suggests that a prominent mechanism of tumor invasion is by the proteolytic destruction of the stromal compartment. However, this does not imply that all invasive tumors show increased stromal aminopeptidase activity, for other enzyme mechanisms not demonstrable by the present technique may be responsible for stromal dissolution in certain tumor types. It is possible that stromal proteolysis may be elicited by a factor elaborated by tumor cells which activates the peptidase, or may represent activation as the result of an immune response. Histochemically demonstrable stromal proteolytic activity may be correlated with the invasive capacity of the tumor, but is not related to its grade of anaplasia or the extent of adjacent fibroplasia. The aminopeptidase activity demonstrated histochemically by using l-leucyl-β-naphthylamide has not been identified as “leucine” aminopeptidase since neither metal-ion dependence nor relative amino acid substrate specificity correlates with that defined by Smith et al. The new modification for the histochemical demonstration of aminopeptidase activity on fresh frozen and frozen-dried tissue sections is compared with a method utilizing an inhibitory, slow-coupling diazonium salt, and the inherent errors in interpretation when using the latter method are described.