CD133: to be or not to be, is this the real question?

CD133 (prominin-1) is a member of the transmembrane glycoprotein family and was initially described as a specific marker to select human hematopoietic progenitor cells. Later it was recognised as an important marker to identify and isolate the specific cell subpopulation termed “cancer stem cells” (CSCs). Many studies showed that CD133+ cells have stemness properties such as self-renewal, differentiation ability, high proliferation and they are also able to form tumors in xenografts. Moreover it has been demonstrated that CD133+ cells are more resistant to radiation and standard chemotherapy than CD133- cells. Despite this other investigations demonstrated that also CD133- cells can show the same characteristics as those positive for CD133+. Hence, some inconsistencies among published data on CD133 function can be ascribed to different causes questioning the main role as specific marker of cancer stem cells. In fact, many authors indicate that CD133 is expressed both in differentiated and undifferentiated cells, and CD133- cancer cells can also initiate tumors. Indeed, it is still a matter of debate whether CD133+ cells truly represent the ultimate tumorigenic population. However, the belief that CD133 may act as a universal marker of CSCs has been met with a high degree of controversy in the research community. In this review there is an attempt to highlight: i) the role and function of CD133, with an overview of the current stage of knowledge regarding this molecule, ii) the difficulty often encountered in its identification iii) the utility of CD133 expression as a prognostic marker.