New Insights into the Cell Biology of Hematopoietic Progenitors by Studying Prominin-1 (CD133)

Abstract

Prominin-1 (alias CD133) has received considerable interest because of its expression by several stem and progenitor cells originating from various sources, including the neural and hematopoietic systems. As a cell surface marker, prominin-1 is now used for somatic stem cell isolation. Its expression in cancer stem cells has broadened its clinical value, as it might be useful to outline new prospects for more effective cancer therapies by targeting tumor-initiating cells. Cell biological studies of this molecule have demonstrated that it is specifically concentrated in various membrane structures that protrude from the planar areas of the plasmalemma. Prominin-1 binds to the plasma membrane cholesterol and is associated with a particular membrane microdomain in a cholesterol-dependent manner. Although its physiological function is not yet determined, it is becoming clear that this cell surface protein, as a unique marker of both plasma membrane protrusions and membrane microdomains, might reveal new aspects of the cell biology of rare stem and cancer stem cells. The aim of this review is to outline the recent discoveries regarding the dynamic reorganization of the plasma membrane of rare CD133+ hematopoietic progenitor cells during cell migration and division.

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

“…Although several putative ovarian CSC markers have been identified (e.g., CD133, ALDH1, CD44, and CD117) (8,18,19,44,45), such markers also can be found on normal adult tissues, including normal stem cells (10,46,47). Therefore, targeting such antigens with mAbs or small molecules also may affect the normal tissues that express these antigens (48,49).…”

CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells

“…11,12). Indeed, CD133 is widely used as a cell surface antigen to prospectively isolate human HSCs that can reconstitute hematopoiesis upon transplantation into mice (13,14), sheep (9), and humans (15).…”

“…17) and solid cancers (18). From a cell biological point of view, CD133 is a unique marker of both plasma membrane protrusions (6,8) and cholesterol-based membrane microdomains (19,20) and could be differentially inherited to daughter cells upon cell division as demonstrated in murine neural stem cells (2), human HSCs (11,12), and human lung and brain cancer cells (21,22). Furthermore, a link between the asymmetric cell distribution of CD133 and the cellular fate has been elegantly demonstrated in neural stem cells (2).…”

Attributes of adult stem cells

“…The specific functions and ligands of the prominins are still relatively unclear, but they are distinct in their restricted expression within plasma membrane protrusions, such as epithelial microvilli [70]. Two antibodies, CD133/1 (also known as AC133) and CD133/2 (also known as AC141) recognize different glycosylated epitopes, and most studies use CD133/1.…”