Revisiting the Role of CD63 as Pro‐Tumorigenic or Anti‐Tumorigenic Tetraspanin in Cancers and its Theragnostic Implications

Abstract

Cluster of differentiation antigen 63 (CD63) belongs to a superfamily of proteins, usually defined as tetraspanins which are known to transverse the bilayer membranes four times. The expression of CD63 has been shown to get altered in several cancers, where it has been demonstrated to act as both a tumor promoter and tumor suppressor. The present review describes the mechanism of how CD63 promotes tumor formation in certain cancer types while inhibiting in some other specific cancers. Glycosylation, a post-translational process plays a significant role in regulating the expression and function of these membrane proteins. Being a crucial exosomal flag protein, CD63 has been found to get involved in endosomal cargo sorting as well as the production of extracellular vesicles. Increased expression of exosomal CD63 derived from advanced tumors has demonstrated its role in promoting metastasis. CD63 also regulates the characteristic and function of stem cells on which they get expressed. This particular tetraspanin has been discovered to participate in gene fusion to perform distinctive roles in certain specific cancer types like breast cancer and pigmented epithelioid melanocytoma. Furthermore, this review mentions twelve different microRNAs obtained from miRDB that might target CD63. A few theragnostic uses of this membrane protein are also discussed. Thereby, the review indicates that further studies on CD63 might prove it to be an effective therapeutic target in different cancers in the coming future.

Post-death Vesicles of Senescent Bone Marrow Mesenchymal Stromal Polyploids Promote Macrophage Aging and Breast Cancer

“…Polyploid giant cancer cells (PGCCs) are believed to be the transformed stem cells driving aggressive growth in solid tumor including BC (37, 38). SASP is shown to favorably transform stem cells and CD63 is identified in cancer stem cells (39), which together with our finding that CD63 is a predominant biomarker of SPSBs, promoted us to test if SPSB-promoted protumorigenesis is associated with PGCC formation. Indeed, karyotyping revealed a time-dependent increase of PGC population ranging from 16.9% to 22.3% in MCF-10AS cells compared to the basal 4.50% PGCs in MCF-10A cells with sham-SPSB culture condition; similarly PGC enhancement from 6.56% in MCF-10A cells to 17.3% PGCCs in MCF-10A cells transformed by overexpressing Her2, 11.3%, and 17.2% in MCF-7 and MDA-MB-231 cells (Supplementary Fig.…”

Transforming native exosomes to engineered drug vehicles: A smart solution to modern cancer theranostics

“…[138] Similarly, neuroblastoma cells release CD63+ exosomes and CD63exosomes. [128] These heterogeneity in the same set of exosomes creates difficulty in specific targeting and drug loading. Also, non-specific delivery of EEx may cause drug accumulation at the off-sites which may cause therapeutic failure.…”

“…Exosomes with glycoproteins like sialic acid and mannose target ovarian cancer cells, Integrins like α6β4 and α6β1 targets advanced NSCLC, αvβ5 targets advanced hepatic cancer and tetraspannin CD63 expressed exosome targets dendritic cells. [126][127][128] Exosomes with selective receptors like CD47 can evade host immunity, increasing the uptake ability. [129]…”