Recently, the role of the neonatal Fc receptor (FcRn) in anti-tumor immunity has been evidenced. The overexpression of FcRn and the accumulation of albumin are observed in tumor tissues. It is assumed that FcRn-mediated albumin recruitment implicates in neoplastic cell growth. Blocking FcRn seems efficient in decreasing the recycling of albumin and interrupting the nutrition transport by albumin to tumor cells. Thus, targeting FcRn has potential efficacy in cancer treatment. Creative Biolabs has successfully established an optimized Magic™ “humanized” animal platform to offer specialty manipulated FcRn knock-in mice for our clients all over the world.
FcRn, a member of the IgG-Fc receptor family, is a heterodimer composing of a β2-microglobulin (B2M) light chain and a major histocompatibility IgG α heavy chain. Studies revealed that FcRn is expressed broadly all over the body. FcRn has dominant expression in endothelial and epithelial cells and is also distributed on dendritic cells (DCs) and macrophages. Importantly, recent studies found that significantly high expression of FcRn appeared in tumor stroma and adjacent tissue DCs in breast, pancreatic, lung, colorectal, ovarian, bladder, renal, head and neck, and cervical cancer.
The uncontrolled cellular proliferation of cancer cells needs large amounts of nutrients. Abundant nutrients are transported through vascular architecture built within the tumor microenvironment. Albumin itself is a well-known amino acid source. Besides, albumin has multiple ligand binding sites, thus, serving as a transporter of endogenous nutrients such as thyroxine and fatty acids. These nutrients provided by albumin is adopted for cellular growth, cellular development, basal metabolic rate, and membrane phospholipid synthesis. Therefore, the utilizing of albumin by cancer cells plays a key role in tumor growth and survival. The concentration of circulatory albumin could be maintained via binding to FcRn.
FcRn plays a critical role in regulating albumin homeostasis. FcRn serves as the endosomal albumin transporter responsible for extending half-lives of albumin. Specifically, in the acidic environment (pH≤6.5) of the endosome, FcRn binds to albumin to salvages albumin from lysosomal catabolism. Afterward, the FcRn-albumin complex transports to the cell surface followed by albumin release back into circulation at the extracellular environment (pH~7.4). Besides, through the transcytosis of FcRn-albumin complexes, the biodistribution of albumin could be also modulated. Significantly higher expression level of FcRn exhibited in human cancer tissues compared with bordering healthy tissues. The overexpression of FcRn could accumulate more albumin which facilities tumor cell growth and survival. Thus, the FcRn-mediated albumin recruitment mechanism could be targeted to inhibit the tumor growth via decreasing the nutrient transportation.
Fig.1 FcRn expression in tumor tissues. (Larsen, 2020)
In vivo studies found tumor growth was accelerated in xenografts using FcRn-expressing HT-29 human colorectal cancer cells. The FcRn expression screening results revealed that human cancer tissues exhibited significantly higher expression of FcRn compared with bordering healthy tissues. The above results suggest the FcRn implicates in the tumor growth and survival. Thus, targeting FcRn is recognized as a relatively novel therapeutic approach in cancer treatment. With advanced technology, Creative Biolabs has provided the humanized FcRn knock-in mice for our global clients and advanced their drug development. If you are interested in this model, please feel free to contact us for more details.
Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:
Reference
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