Original Article CD133, Trop-2 and α2β1 integrin surface receptors as markers of putative human prostate cancer stem cells

Introduction The origin of prostate cancer (PrCa) is still a matter of debate in the scientific community [1]. The three specific lineages (basal, luminal and neuroendocrine) of the normal prostatic epithe-lium [2] result from the directional differentia-tion of normal stem cells (NSCs) [3]. The vast majority of PrCa cells has a luminal phenotype, but unlike normal luminal cells that are termi-nally differentiated and have limited prolifera-tive capacity, PrCa cells still retain the ability to proliferate, resembling “basal” characteristics [4]. To date, two major theories have been pro-posed to explain the initiation of PrCa [5]. First, PrCa may arise from niches of NSCs that are localized in the basal layer of prostate glands [2, 6]. Under physiological conditions, these low-proliferating NSCs can give rise to a second population of more rapidly cycling cells, known as transit amplifying cells [7], which differenti-ate into mature, secretory cells [2]. However, during tumorigenesis genes able to tightly con-trol cell proliferation or DNA damage repair in NSCs can accumulate “transforming” muta-tions, resulting in the conversion to cancer stem cells (CSCs) that show growth advantages over their normal counterparts [8, 9]. A second the-ory postulates that PrCa can originate from nor-mal cells in the luminal/transit amplifying layer, that re-acquire abilities for self-renewal, initiat-ing the uncontrolled tumor growth [10]. CSCs, also designated cancer stem/progenitor cells [11], are defined as cells with the special ability to generate tumors when injected in ani-mal hosts [12] through processes of self-renewal and differentiation into the multiple Am J Transl Res 2010;2(2):135-144 www.ajtr.org /AJTR1003002