Mouse Orthotopic Xenographs of Human Prostate Primary Tumors

摘要

Currently, primary human tumor material is insufficient due to small size, multifocality and difficulty of visualization at macroscopic examination. This essentially prevents extensive studies aimed at distinguishing indolent and aggressive organ-confined prostate cancers. Understanding the molecular alterations governing tumorigenesis and cancer progression is the first step necessary for the design of effective and targeted therapies. For this reason, in recent years considerable efforts have been devoted to generate clinically relevant models of prostate tumors. As a result, a number of cell lines and in vivo models have been developed. To date, however, there is no model in which all aspects of human PCa progression can be mimicked. It is important to note that the overwhelming majority of organ-confined human prostate cancers display a luminal phenotype, characterized by expression of androgen receptor (AR), PSA and luminal-type keratins. The established human cell lines most commonly utilized in prostate cancer research are derived from metastases and only few of them are androgen-sensitive. In the last 20 years a variety of methodologies have been attempted for the purpose of establishing primary epithelial cell cultures displaying a luminal phenotype reflective of the human primary prostate tumor of origin, but attempts have been largely unsuccessful. The possibility exists that small populations of contaminating nonmalignant cells (invariably present in the human tissue sample) can populate and ultimately replace transformed cells in vitro. When transformed cells are indeed obtained from prostate primary adenocarcinomas they rarely form tumors in nude mice. Finally, primary cells from prostate cancers are mostly diploid and do not show relevant chromosomal alterations.