Introduction

Latest statistics based on GLOBOCAN 2008, the standard set of worldwide estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer (IARC), revealed that prostate cancer (PC) is the most commonly diagnosed malignancy and the second leading cause of cancer-related mortality in male in developed countries [1]. The options in the treatment of PC are surgical tumor resection, hormonal therapy, radiotherapy, and adjuvant chemotherapy. These therapies, alone or in combination, show beneficial effects and a significant curative rate in treating patients with localized PC in the early stages. However, the development of locally advanced and/or metastatic hormone-refractory prostate cancers (HRPCs) eventually results in disease recurrence. Most patients who undergo potentially curative resection for advanced and/or metastatic HRPCs subsequently relapse due to the persistence of foci and micro-metastases. Therefore systemic chemotherapy may represent another option to eradicate the PC cells, including the highly tumorigenic stem/ progenitor cells that can drive tumor growth at primary neoplasms and distant meta-static sites.

The existence of stem cells (SCs) was firstly demonstrated by James Till and the late Ernest McCulloch in 1963 in their earlier work on the radiation sensitivity of mouse bone marrow cells by showing that limited numbers of cells could give rise to clonal colonies of erythroid and myeloid cells in the spleens of the irradiated hosts [2]. Although, much improvement has been achieved in the development of methods to kill cancer cells that form a variety of malignancies; nevertheless, relapse is an ongoing problem along with the development of metastatic tumors at sites remote from that of the original tumor. One suggestion to account for these phenomena is the existence of a stem cell with tumorigenic properties capable of regenerating all the differentiated cell types presented in the original tumor. The key paper supporting the cancer stem cell (CSC) hypothesis from the laboratory of John Dick appeared in 1997, in which they demonstrated that an isolated cell type was capable of initiating acute myeloid leukemia (AML) [3]. With the knowledge provided by the science of stem cell biology, the Nobel Prize in Physiology or Medicine in the year 2007 was awarded jointly to Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells".

Stem cells possess some unique properties: a) they are undifferentiated and unspecialized; b) they are able to multiply for long periods while remaining undifferentiated (slowly cycling); c) they are capable of differentiating into specialized cells of a particular tissue (produce progeny in at least two lineages); and d) they can be serially transplanted. The combination of these properties is often referred to as "stemness" [4]. Stem cells can divide symmetrically or asymmetrically. A symmetrical division occurs when two daughter cells share the same stem cell features and happens when their numbers (stem cell pool) need to be expanded, such as during embryonic development or after tissue injury. An asymmetrical division occurs when one of the progeny remains undifferentiated, thereby replenishing the pool of SCs, while the other daughter cell can proliferate and differentiate into specialized cells to generate new tissue mass.

Stem cells have long been implicated in prostate gland formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggested that those stem cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of PC also indicate that it originates from stem cells. In this chapter, the biological and clinical implications of stem cells in prostat-ic carcinogenesis and the involvement of prostate cancer stem cells (PCSCs) in the many faces of PC are demonstrated and summarized. The theory of a stem cell origin of cancers represents a major paradigm shift that may completely revamp to diagnosis, monitoring, and therapy of PC.

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