PROSTATE TUMOR-CELL INVASION - A COMPARISON OF ORTHOTOPIC AND ECTOPICMODELS

Interest in orthotopic models has been generated by recent reports of increased invasive and metastatic potential demonstrated by tumor cell lines following injection into their tissue of origin rather than sub cutaneously. We have previously demonstrated that transfection of the tumorigenic human prostate cell line, Du-145, with the metalloproteina se matrilysin increased its ability to invade the diaphragm following an intraperitoneal injection. In this study we compare the invasive an d metastatic behavior of transfected Du-145 cell lines injected into t he dorsal lateral lobe of the prostate to that observed when they are injected intraperitoneally. Immunohistochemistry was used to examine 3 7 orthotopically injected severe combined immunodeficient mice for loc al invasion and metastatic lesions. In addition, the effect of injecti on site on the level of expression of four genes thought to influence the invasiveness of tumor cells (matrilysin, stromelysin, TIMP-1, and TIMP-2), was determined by northern analysis of orthotopic and subcuta neous tumor tissue. The results demonstrate that the level of mRNA exp ression of the genes examined was similar at the two sites of injectio n and that the invasive properties of Du-145 cells following orthotopi c implantation were comparable to that observed on the diaphragm follo wing intraperitoneal injection. The advantages of the diaphragm invasi on model are: less procedure-related mortality, ease of cell delivery, and provision of an easily orientated structure in which the earliest penetration of a basal lamina can be observed.