The biological role and immunotherapy of gangliosides and GD3 synthase in cancers

Abstract

Gangliosides are a large subfamily of glycosphingolipids that broadly exist in the nervous system and interact with signaling molecules in the lipid rafts. GD3 and GD2 are two types of disialogangliosides (GDs) that include two sialic acid residues. The expression of GD3 and GD2 in various cancers is mostly upregulated and is involved in tumor proliferation, invasion, metastasis, and immune responses. GD3 synthase (GD3S, ST8SiaI), a subclass of sialyltransferases, regulates the biosynthesis of GD3 and GD2. GD3S is also upregulated in most tumors and plays an important role in the development and progression of tumors. Many clinical trials targeting GD2 are ongoing and various immunotherapy studies targeting gangliosides and GD3S are gradually attracting much interest and attention. This review summarizes the function, molecular mechanisms, and ongoing clinical applications of GD3, GD2, and GD3S in abundant types of tumors, which aims to provide novel targets for future cancer therapy.

Targeted therapies in retinoblastoma: GD2-directed immunotherapy following autologous stem cell transplantation and evaluation of alternative target B7-H3

“…In patient 3 a GD2-negative relapse occurred. Loss of GD2 is a rare event in neuroblastoma following anti-GD2 immunotherapy [ 21 , 35 ] and can be partly explained by reduced antigen production or by internalization of antigen/antibody complexes [ 36 , 37 ]. In our patient, theoretically a separate GD2-negative retinoblastoma could have developed on the basis of the RB1 germline mutation, independent from the immunotherapy.…”

GD2 and its biosynthetic enzyme GD3 synthase promote tumorigenesis in prostate cancer by regulating cancer stem cell behavior

“…( A ) Schematic of key GD2 biosynthetic steps displaying the enzymes ( ST3GAL3, ST8SIA1 and B4GALNT1 ) and intermediate products (GM3 and GD3) [Adapted from (45)]. LNCaP C4-2 cells with stable knockdown (KD) of p53 or RB1, previously shown to undergo NE differentiation, were compared with parental cells.…”

Astaxanthin alleviates ganglioside metabolism disorder in the cortex of Alzheimer's disease mice

“…2 Abnormal changes in N-glycolylneuraminic acid (NeuGc) occurred in some human tissues that are inflammatory or cancerous. 5 As per the standard naming rules, G indicates a GLS structure, M/D/T/Q/P/H/S indicates the number of sialic acid units (1)(2)(3)(4)(5)(6)(7), and the difference obtained by subtracting the glycosyl number from the 5 represents the number of glycogroups in GLSs. The function of GLS may be related to the amount of sialic acid.…”

“…E-mail: xujie9@ouc.edu.cn, songyu@ouc.edu.cn, wzg940518@163.com, wangxx0416@163.com, myx1045941257@163.com, congpeixu@ouc.edu.cn, cen0812@163.com, xuech@ouc.edu.cn; Fax: +86-532-82032597; Tel: +86-532-82032597 b Qingdao Marine Science and Technology Center, Qingdao, Shandong Province 266235, China various cancers is predominantly upregulated and the increased expression is involved in tumor proliferation, invasion, metastasis, and immune responses. 7 GT 1b is vital for increasing the porcine oocyte nuclear maturation rate and decreasing intracellular ROS levels during in vitro maturation. 8 GQ 1b is strongly associated with oculomotor weakness in Guillain-Barre syndrome and Miller-Fisher syndrome.…”

“…6 The expression of GD 3 and GD 2 in various cancers is predominantly upregulated and the increased expression is involved in tumor proliferation, invasion, metastasis, and immune responses. 7 GT 1b is vital for increasing the porcine oocyte nuclear maturation rate and decreasing intracellular ROS levels during in vitro maturation. 8 GQ 1b is strongly associated with oculomotor weakness in Guillain–Barre syndrome and Miller–Fisher syndrome.…”