Modelling cancer: recapitulation of tumor growth in experimental systems in vivo and in vitro

The purpose of the study was to evaluate model systems of cancer development and compare some of their critical features with cancer development in vivo. Ovarian and endometrial cancers in man were used as correlates. Tumor development in experimental animals, exposed to carcinogens and UV irradiation, showed the entire spectrum of tumor development as compared to spontaneous carcinomas: hyperplasia, dysplasia, benign papillomas and malignant squamous cell carcinomas. For short-term analysis of differentiated homogenous cell populations, the transplant model proved most useful. For long term analysis of effects of extraneous agents, the skin carcinogenesis model is probably the most rewarding. Analysis of proliferation markers in human tumor samples as studied by immunohistochemistry, showed that an increased expression of PCNA and Ki-67 was associated with poor prognosis in ovarian neoplasms. Analysis of cell proliferation in model tumors showed that the transplant model has a better sensitivity when compared to the animal skin model and the subcutaneous injection model, in that effect of changes in cell-host interaction on the location and extent of the proliferating cell population can be studied therein. The expression of some growth factors, their receptors, oncogenes and suppressor genes were studied in ovarian and endometrial carcinomas and in skin cancer model system in mouse exposed to carcinogens and UV irradiation. Variability in expression and methodological problems precluded detailed analysis of these markers in different models. The expression of TGFβ1, TGFβ2 and TGFβ3 was determined in normal human keratinocytes, and in 7 immortalized and ras-transfected benign and malignant keratinocyte cell lines, maintained as transplants and as subcutaneous tumors in nude mice. By differential immunohistochemical localization of TGFβ isoforms, we demonstrated that each isoform may serve specific roles in tumor development and progression. The complex nat