hCG and Hyperglycosylated hCG Carbohydrate Structure Corrected

Abstract

Multiple articles have been published describing the N-linked and O-linked oligosaccharide structures of hCG. All, however, have used purified preparation from pregnancy urine and from choriocarcinoma patient urine. This has told the scientific community that pregnancy and choriocarcinoma hCG-related molecules contain Type 1 and Type 2 O-linked oligosaccharides and biantennary and triantennary N-linked oligosaccharide. Recent years have seen the demonstration of two completely independent hCG molecules, hCG and hyperglycosylated hCG. hCG is a pregnancy hormone made by syncytiotrophoblast cell. Hyperglycosylated hCG is a TGFß receptor binding autocrine produced by cytotrophoblast cells. The two independent share a common amino acid sequence and just vary in carbohydrate structure. Unfortunately, all the carbohydrate structure reports are on a mixture of hCG and hyperglycosylated hCG, as present in pregnancy and choriocarcinoma. This does not all anyone to clearly see the carbohydrate structural differences between the two molecules. Here we carefully examine the carbohydrate structural differences between hCG and hyperglycosylated hCG using the B152 hyperglycosylated hCG-specific immunoassay. It is shown that hCG has only Type 1 O-linked oligosaccharides, while hyperglycosylated hCG only has Type 2 O-linked oligosaccharides. Type of O-linked oligosaccharide structure completely distinguishes hCG and hyperglycosylated hCG.

The Minute Structural Difference between the Hormone hCG and the Autocrine Hyperglycosylated hCG

“…The hormone hCG, in contrast, which is very slowly nicked and very slowly dissociated, must not be nicked or dissociated for maximal hormone LH/hCG receptor response [26][27][28]30]. The receptor only binds non-nicked intact hormone hCG.…”

hCG, Hyperglycosylated hCG, Pituitary hCG, Cancer hCG and Fetal hCG

“…We can tell nothing from this route structure about what differentiates hCG-1, hCG-2, hCG-3, hCG-4 or hCG-5. [9] and the recent corrections of Cole [10]. ND is not determined.…”

“…The predicted model is a variation on hCG-1 based on this observation. Research studies show that hCG-2 has type 2 O-linked oligosaccharides and biantennary N-linked oligosaccharides [9,10]. Studies show that cancer hCG (hCG-4) is analogous to hCG-2, both binding a TGFß receptor but has, as shown in Figure 3 triantennary N-linked oligosaccharides [10].…”

“…This physically drives cancers, blocking apoptosis, promoting cancer cell growth and promoting cancer cell invasion of neighboring cells [18][19][20]. Trophoblastic malignancies, choriocarcinoma, testicular germ cell malignancies and ovarian germ cell malignancies (germ cells cancer take on trophoblastic morphology) produce hCG-4, while all other cancers cannot combine subunits [34], and produce hCG-4 free ß-subunit [9,10,18,19].…”

“…There is a specific antibody for measuring molecules with type 2 O-linked sugar side chains, hCG-2, hCG-4 and hCG-4 free ß-subunit, but that is it. The existence of the six semi-independent molecules was demonstrated by structure studies [9,10,46]. Bold underline poor detection 6 of 9 5 of 9 6 of 9 7 of 9 5 of 9 5 of 9 7 of 9 7 of 9 1 of 9 7 of 9 6 of 7 LH crossreactivity 0.01% 0.01% 0.01% 0.01% 0.32% 0.01% 0.01% 0.01% 0.04% 0.53% 0.01% Table 9: Detection of serum hCG-related molecules by different automated total hCG tests (40,41).…”