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Aminopeptidase M and dipeptidyl peptidase IV activity in epithelial skin tumors: a histochemical study
M C Moehrle1, B E Schlagenhauff, C Klessen
1Department of Dermatology, University of Tuebingen, Germany.
Abstract:
The activities of microsomal alanylaminopeptidase (APM EC 3.4.11.2) and of dipeptidyl dipeptidase IV (DPP IV EC 3.4.14.5) were histochemically studied in frozen sections of normal skin, seborrheic keratosis, basal cell carcinoma, solar keratosis, Bowen's disease and squamous cell carcinoma using amino acid- or peptide-4-methoxy-2-naphthylamides as specific chromogenic substrates. Compared to biochemical and immunohistochemical methods, the histochemical technique used in this study allows distinct localization of protease activity within the tumor tissue and the tumor-associated stroma. Strong APM activity was detectable only in the stroma of basal cell carcinoma, a result which reflects the particular tumor-stroma interaction of this semimalignant tumor. APM activity was not detectable in either healthy epidermis or the tumor parenchyma. Altered activity of DPP IV was found in the tumor cells as well as in the surrounding connective tissue: precancerous dermatoses and basal cell carcinomas had higher levels of DPP IV-activity than normal skin or benign seborrheic keratosis. Poorly differentiated malignant squamous cell carcinomas, however, showed no histochemically detectable DPP IV-activity at all. This result is in line with reports of decreased activity of this enzyme in cases of malignancy.
Insights
Histochemical analysis revealed distinct protease activities in skin tumors. Alanylaminopeptidase (APM) was found in basal cell carcinoma stroma, while dipeptidyl dipeptidase IV (DPP IV) activity varied with cancer type and differentiation.
Area of Science:
- Biochemistry
- Dermatopathology
- Enzymology
Background:
- Microsomal alanylaminopeptidase (APM) and dipeptidyl dipeptidase IV (DPP IV) are enzymes with roles in cellular processes.
- Altered enzyme activity is often associated with neoplastic transformations in various tissues, including skin.
Purpose of the Study:
- To histochemically investigate the activity and localization of APM and DPP IV in normal skin and various skin neoplasms.
- To correlate enzyme activity patterns with specific tumor types and differentiation states.
Main Methods:
- Histochemical staining of frozen skin sections from normal skin and various skin lesions (seborrheic keratosis, basal cell carcinoma, solar keratosis, Bowen's disease, squamous cell carcinoma).
- Utilized specific chromogenic substrates (amino acid- or peptide-4-methoxy-2-naphthylamides) for APM and DPP IV detection.
- Employed a histochemical technique for precise localization of protease activity within tumor tissue and stroma.
Main Results:
- Strong APM activity was exclusively detected in the stroma of basal cell carcinoma, indicating a specific tumor-stroma interaction.
- APM activity was absent in healthy epidermis and tumor parenchyma.
- DPP IV activity was elevated in tumor cells and connective tissue of precancerous dermatoses and basal cell carcinomas compared to normal skin and seborrheic keratosis.
- Poorly differentiated squamous cell carcinomas exhibited no detectable DPP IV activity, consistent with decreased enzyme levels in malignancy.
Conclusions:
- Histochemistry provides distinct localization of APM and DPP IV activity in skin tumors and their microenvironment.
- APM's stromal localization in basal cell carcinoma highlights unique tumor-stroma interactions.
- DPP IV activity patterns correlate with skin lesion type and malignant progression, with decreased activity in poorly differentiated squamous cell carcinomas.