Abstract
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 nature of TGFβ expression prevented detailed
analysis of isozymes in different models, the results in this study, however,
indicated a similar pattern in the models analyzed.
Morphological methods were used to determine relationship between epithelial
growth and formation and deposition of collagens in the extracellular matrix in
experimental models and human tumors. The composition of the mesenchyme differed
in tumors originating from different cell lines reflecting functional
interaction between epithelial cells and the mesenchyme in neoplastic
development. Tumor-stroma interaction was distinct in human, comparable
alterations were observed in experimental models, more so in transplants, less
in subcutaneous tumors, affecting tumor growth and differentiation in the
different models.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5643-3 |
| Date | 04 May 2000 |
| Creators | Jussila, T. (Tommi) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2000 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
Page generated in 0.0021 seconds