Looking out for cancer stem cells' properties: the value-driving role of CD44 for personalized medicines.
The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44⁺ cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.
Sara
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Horta
Ana Lúcia
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Agostinho
Rita
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Mateus
Lucília
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Pereira
Carolina
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Pereira
Liliana
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Capinha
Slavomira
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Doktorovova
Alexandra
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Brito
Faculdade de Farmácia da Universidade de Lisboa Faculty of Pharmacy of the University of Lisbon, Intracellular Trafficking Modulation for Advanced Drug Delivery (InTraCell_ADD) research group, iMed.UL - Research Institute for Medicines and Pharmaceutical Sciences, Av. Prof. Gama Pinto 1649-003, Lisbon, Portugal. mvideira@ff.ul.pt.
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Videira
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D019317:Evidence-Based Medicine; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D057285:Precision Medicine
D000970:Antineoplastic Agents; D015415:Biomarkers; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins