INVIVO AND INVITRO APPROACHES TO STUDY METASTASIS IN HUMAN PROSTATIC-CANCER

Prostate cancer is the most common malignancy in American males and is second only to lung cancer as a cause of death in the United States. Clinically, radical prostatectomy offers a patient with locally contained disease an excellent chance for cure. For patients with metastatic disease. the current therapies are merely palliative. Understanding the biology of prostate cancer metastasis should facilitate the development of novel and effective therapeutic modalities. Crucial to this objective is the availability of human tumor systems in which the biology of metastasis can be studied. The present chapter will briefly assess various in vivo and in vitro approaches to study metastasis in human prostate cancer. Utilization of athymic nude mice has played an important role in maintaining human prostatic cancer cells as xenografts and has provided an opportunity to establish site-specific subpopulations of the parental cell lines for further characterization and investigation. At present, a few established cell lines have been useful for this purpose. Fresh tumor specimens, unfortunately, have shown limited ability to grow in nude mice. The recent development of novel approaches to permit the maintenance of freshly harvested prostate cancers has been encouraging. The use of reconstituted basement membrane (Matrigel) for co-injection with cancer cells into the subcutaneous tissues has supported growth of biologically indolent tumors. Another approach is to administer tumor cells orthotopically into the prostate of recipient nude mice. Bone marrow metastases in nude mice have been rare in the past. Recently, three approaches have been shown to be successful in accomplishing bony metastasis with PC-3 cells. They include intrasplenic injection, tail vein injection with vena cava occlusion, and tail vein injection into SCID (severe combined immunodeficient) mice. Other routes of tumor cell injection are also useful for the establishment of various organ-related metastatic subpopulations derived from unselected parental cell lines. The use of a modified Boyden chamber assay system has offered a rapid in vitro assessment of the invasive potential of specific cancer cell lines. The various in vivo and in vitro approaches described in the present chapter make it possible to enrich site-specific variants of different prostatic cancer cell lines for further characterization and elucidation of the molecular mechanisms underlying metastasis in prostate cancer. These approaches also provide an opportunity for testing and developing novel therapeutic modalities.