Glycohistochemical monitoring of chemically induced sarcomas at different stages of tumorigenesis.

Malignant soft tissue tumors still represent a source of uncertainty and controversy concerning histogenetic origin and histological behavior. Considering this, chemically induced sarcomas furnish an attractive model for the elucidation of cellular alterations during tumorigenesis. This approach allows us to closely follow cyto- and histological changes within coherent stages of tumor development. The specimen under scrutiny comprised 35 rat tissue samples from day 10 up to day 200 after benzo[a]pyrene injection. Additionally, for comparison and validation two human malignant fibrous histiocytomas (MFH) were investigated. The essential biological significance of protein-carbohydrate interactions warranted the histochemical application of synthetic tools (neo-glycoproteins-NGP) and lectins in order to reveal phenotypical dynamics in this aspect throughout the process of tumor development. Namely, 6 plant lectins (carbohydrate-binding proteins with defined saccharide specificity), 7 custom-made synthetic NGP (as the corresponding ligands visualizing endogenous lectins) and additionally three antibodies were employed. Characteristic cell populations were histochemically demonstrated in four stages of tumor development: exudation (n = 5), mesenchymal proliferation (n = 7), atypical granulation tissue (n = 7) and sarcoma (n = 16). Changes of glycohistochemical binding patterns were in close phenotypic relation to cellular activity, differentiation, local distribution as well as malignant transformation and tumor progression. At present, the new glycobiological features of the malignant phenotype substantiate the assumption that not only glycosylation but also the receptor display is altered upon carcinogenesis. In conclusion, this chronological longitudinal study takes advantage of the combination of a coherent model of tumorigenesis with innovative histochemical tools whose ligands are supposed to act as mediators of cell-cell- and cell-matrix interactions. It clearly demonstrates the suitability of the glycohistochemical method for comparative approaches. The systematic analysis of glycohistochemical determinants will improve our understanding of the early tumor biological processes with potential implications for therapeutic interventions.