Prominosomes - a particular class of extracellular vesicles containing prominin-1/CD133?

Extracellular membrane vesicles (EVs) offer promising values in various medical fields, e.g., as biomarkers in liquid biopsies or as native (or bioengineered) biological nanocarriers in tissue engineering, regenerative medicine and cancer therapy.

Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease.

Prominin-1 (CD133) is a cholesterol-binding membrane glycoprotein selectively associated with highly curved and prominent membrane structures. It is widely recognized as an antigenic marker of stem cells and cancer stem cells and is frequently used to isolate them from biological and clinical samples. Recent progress in understanding various aspects of CD133 biology in different cell types has revealed the involvement of CD133 in the architecture and dynamics of plasma membrane protrusions, such as microvilli and cilia, including the release of extracellular vesicles, as well as in various signaling pathways, which may be regulated in part by posttranslational modifications of CD133 and its interactions with a variety of proteins and lipids.

Extracellular lipidosomes containing lipid droplets and mitochondria are released during melanoma cell division.

Background: The incidence of melanoma is increasing worldwide. Since metastatic melanoma is highly aggressive, it is important to decipher all the biological aspects of melanoma cells. In this context, we have previously shown that metastatic FEMX-I melanoma cells release small (< 150 nm) extracellular vesicles (EVs) known as exosomes and ectosomes containing the stem (and cancer stem) cell antigenic marker CD133.

Prominin-1 expression in the testis/epididymis and fertility.

The contribution of Prominin-1 (aka CD133) to male fertility has recently been (re)investigated, with contradictory results. Early findings, essential for deciphering its role, have unfortunately been neglected. Here, the authors present what is currently known about its expression in the male reproductive system of rodents and men so that its involvement in male fertility can be re-examined and discussed in the light of these elements.

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3.

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies.

Prominin-1/CD133: Lipid Raft Association, Detergent Resistance, and Immunodetection.

The cell surface antigen prominin-1 (alias CD133) has gained enormous interest in the past 2 decades and given rise to debates as to its utility as a biological stem and cancer stem cell marker. Important and yet often overlooked knowledge that is pertinent to its physiological function has been generated in other systems given its more general expression beyond primitive cells. This article briefly discusses the importance of particular biochemical features of CD133 with relation to its association with membrane microdomains (lipid rafts) and proper immunodetection.

Human prominin-1 (CD133) is detected in both neoplastic and non-neoplastic salivary gland diseases and released into saliva in a ubiquitinated form.

Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma.

Prominin-2 and Other Relatives of CD133.

Several molecules related to prominin-1/CD133, which was first characterized as a marker of mouse neuroepithelial stem cells and human hematopoietic stem cells, have been identified in various species. In mammals, a second prominin gene, prominin-2, has been identified and characterized, whereas in nonmammalian species, up to three prominin genes are potentially expressed. The structural similarities between prominin-1 and prominin-2 are, to some extent, reflected by their biochemical properties; both proteins are selectively concentrated in specific plasma membrane subdomains that protrude into the extracellular space and are released in small extracellular membrane vesicles.

Prominin-1 (CD133): Molecular and Cellular Features Across Species.

Our knowledge of the first member of the prominin family is growing rapidly as the clinical value of prominin-1 (CD133) increases with its ever-wider use as a stem cell marker in normal and cancer tissues. Although the physiological function of this evolutionally conserved pentaspan membrane glycoprotein remains elusive, several studies have revealed new biological features regarding stem cells, cancer stem cells, and photoreceptors. The wide expression of CD133 in terminally differentiated epithelial cells, long overlooked by many authors, has attracted significant interest through the extensive investigation of human PROMININ-1 as a potential target for cancer therapies in various organs.

CD133 as a biomarker for putative cancer stem cells in solid tumours: limitations, problems and challenges.

The cancer stem cell (CSC) hypothesis, despite the limitations of the currently available models and assays, has ushered in a new era of excitement in cancer research. The development of novel strategies for anti-tumour therapy relies on the use of biomarkers to identify, enrich, and/or isolate the cell population(s) of interest. In this context, various cell characteristics and antigen expression profiles are discussed as surrogate markers.

CD133 and membrane microdomains: old facets for future hypotheses.

Understanding all facets of membrane microdomains in normal and cancerous cells within the digestive tract is highly important, not only from a clinical point of view, but also in terms of our basic knowledge of cellular transformation. By studying the normal and cancer stem cell-associated molecule CD133 (prominin-1), novel aspects of the organization and dynamics of polarized epithelial cells have been revealed during the last decade. Its association with particular membrane microdomains is highly relevant in these contexts and might also offer new avenues in diagnosis and/or targeting of cancer stem cells.

Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.

Besides being a marker of various somatic stem cells in mammals, prominin-1 (CD133) plays a role in maintaining the photoreceptor integrity since mutations in the PROM1 gene are linked with retinal degeneration. In spite of that, little information is available regarding its distribution in eyes of non-mammalian vertebrates endowed with high regenerative abilities. To address this subject, prominin-1 cognates were isolated from axolotl, zebrafish and chicken, and their retinal compartmentalization was investigated and compared to that of their mammalian orthologue.

Prominin-1 (CD133) is not restricted to stem cells located in the basal compartment of murine and human prostate.

Background: Rodent and human prominin-1 are expressed in numerous adult epithelia and somatic stem cells. A report has shown that human PROMININ-1 carrying the AC133 epitope can be used to identify rare prostate basal stem cells (Richardson et al., J Cell Sci 2004; 117:3539–3545).

Prominin-2 is a novel marker of distal tubules and collecting ducts of the human and murine kidney.

Prominin-1 (CD133) and its paralogue, prominin-2, are pentaspan membrane glycoproteins that are strongly expressed in the kidney where they have been originally cloned from. Previously, we have described the localization of prominin-1 in proximal tubules of the nephron. The spatial distribution of prominin-2, however, has not yet been documented in the kidney.

Prominin-1: a distinct cholesterol-binding membrane protein and the organisation of the apical plasma membrane of epithelial cells.

The apical plasma membrane of polarized epithelial cells is composed of distinct subdomains, that is, planar regions and protrusions (microvilli, primary cilium), each of which are constructed from specific membrane microdomains. Assemblies containing the pentaspan glycoprotein prominin-1 and certain membrane lipids, notably cholesterol, are characteristic features of these microdomains in apical membrane protrusions. Here we highlight the recent findings concerning the molecular architecture of the apical plasma membrane of epithelial cells and its dynamics.

Expression of distinct splice variants of the stem cell marker prominin-1 (CD133) in glial cells.

Prominin-1 (CD133) is a cholesterol-interacting pentaspan membrane glycoprotein specifically associated with plasma membrane protrusions. Prominin-1 is expressed by various stem and progenitor cells, notably neuroepithelial progenitors found in the developing embryonic brain. Here, we further investigated its expression in the murine brain.

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder.

Although the male reproductive system seems to be enriched in transcripts encoding for both Prominin genes, little is known about their spatial distribution in distinct segments of this organ system. This is especially true for the less-characterized second Prominin paralogue, Prominin-2. The present study, therefore, mainly examines the expression of Prominin-2 in male mice and reveals the existence of some crucial differences in the tissue compartmentalization of the two Prominin paralogues in the testis, epididymis, seminal vesicle, prostate and urinary bladder.