Mon, 03/03/2014 - 15:18

Also known as PROM1 and AC133, this gene is located on chromosome 4p15 and encodes CD133, a 120kDa pentaspan transmembrane glycoprotein (5-TM) and presents multiple spliced variants. Prominin-1 (CD133) was the first protein identified as "Prominin"; originated from the Latin word "Prominere" meaning to protrude and was initially detected on CD34 bright hematopoietic stem cells using a monoclonal antibody (mAb) raised against human CD34+cells. This antibody detected the AC133 epitope of CD133 and since the expression of this epitope was restricted to CD34+ progenitors in bone marrow, adult blood and fetal liver cells, CD133 was proposed as the marker for progenitor hematopoietic cells. [1,2] Subsequently Florek et al, demonstrated the expression of CD133 in several adult human tissues, such as kidney proximal tubules and the parietal layer of Bowman's capsule of juxtamedullary nephrons using a novel CD133 antibody (ahE2). This study proved that AC133 antibody failed in detecting CD133 in adult tissues due to its glycosylation dependent epitope (AC133) which is restricted to stem cells in normal adult tissue. Since the antibodies typically used for CD133 (AC133 and AC141 mAbs) recognize glycosylated epitopes, the possibility remains that the glycosylation status of CD133, rather than expression of the CD133 protein itself, can act as an indirect marker of the CSC phenotype.  [3]

Structurally this protein is characterized by extracellular N-terminus, two large extracellular loops, five transmembrane domains, two small cysteine-rich cytoplasmic loops, and a cytoplasmic C-terminus. [1,2]. Although CD133 was initially described as a specific marker to human hematopoietic progenitor cells, later studies demonstrated it as an important marker to identify and isolate the specific cell subpopulation termed “cancer stem cells” (CSCs) as CD133+ cells showed stemness properties such as self-renewal, differentiation ability, high proliferation, the ability to form tumors in xenografts and substantial resistance to radiation and chemotherapy compared to CD133-. However, CD133’s role as a specific marker of cancer cells is still a matter of debate as other investigations indicate that CD133 is expressed in both differentiated and undifferentiated cells. [1]

Currently neither the ligands nor the function of this protein is fully known.  A recent report by Marzesco in the book by D. Corbeil shows prominin-1 directly interacts with plasma membrane cholesterol within a distinct cholesterol-based membrane microdomain. It is specifically concentrated in plasma membrane protrusion as at the apical plasma membrane of neural cancer stem cells (NSCs) and other epithelial cell. This study as well as other observations suggest a significant role for CD133 as the organizer of the plasma membrane topology. [1] Other studies have linked CD133 to Circulating Tumor Cells (CTCs) which is represented as a potential prognostic biomarkers and a reliable mean to predict metastasis development. [4] Despite all these findings, the exact molecular mechanism and function of CD133 especially in tumor formation and metastasis is yet to be identified.

  1. PMID: 24093054
  2. PMID: 9389721
  3. PMID: 15558321
  4. PMID: 23050098

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