A clarification was needed regarding the name of progastrin, a protein most of the time associated to its historical function as the gastrin precursor when it is intracellular. When it is extracellular (the case for cancer patients), it is no more a precursor of gastrin, it becomes oncogenic and tumor promoter.
We decided to name extracellular progastrin hPG80 to avoid confusion.
1905>1987: From Gastrin to Progastrin
Identification of the intracellular precursor of Gastrin
The story of progastrin started with the discovery of gastrin in 1905 when John Sydney Edkins showed the existence of a hormone responsible for gastrin acid secretion. This hormone was called gastric secretin, or gastrin.
But it is only in 1987 and 88 that the precursor of gastrin was identified and labelled as progastrin, because of its role as a pro-hormone. It is an 80 amino-acid peptide, processed in the endoplasmic reticulum, with gastrin being the final active product of progastrin maturation.
In physiology, progastrin is mainly expressed in the stomach, where gastrin is secreted from the G cells of the antrum. The major function of gastrin is to regulate acidic secretion.
Therefore, for years, progastrin was only known as the precursor of gastrin.
1990>2020: From the gastrin precursor to the oncogenic tumor promoter
Extracellular, "Progastrin" is no longer the precursor of Gastrin, it is an oncogenic protein.
In 1990, the first link of progastrin with tumor cells was done. Bardram was the first to hypothesize that “a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease” (Bardram, 1990).
And this is where the story of progastrin starts, independently of that of gastrin.
Progastrin was shown to be poorly processed in colorectal cancer (Ciccotosto, 1995; Finley et al., 1993; Imdahl et al., 1995; Kochman et al., 1992; Nemeth et al., 1993; Singh, 1994; Van Solinge et al., 1993b). And soon after, Singh et al demonstrated that progastrin was secreted from these cells cultured in vitro, opening the door to the analysis of a functional autocrine/ paracrine function of progastrin in tumor cells (Singh, 1994; Van Solinge et al., 1993b). Colorectal cancers are not the only cancer type to express progastrin. Ovarian cancers do it also (van Solinge et al., 1993a) as well as liver tumors that express precursor forms of gastrin, in particular progastrin unlike normal liver (Caplin et al., 1999). Pancreatic tumors also express the gastrin gene, with 91% of the tumors with the unprocessed progastrin product (Caplin, 2002).
The evidence showing that progastrin could be detected and quantified in the blood of colorectal cancer patients was demonstrated by Siddheshwar et al as early as 2000 (Siddheshwar et al., 2000), later confirmed by Prieur et al (2017). It was also demonstrated that progastrin had to be released from tumor cells in order to exert its oncogenic functions.
The presence of progastrin in the blood of cancer patients was extended to 11 different cancers (You et al, 2020), highlighting the potential that progastrin may have in cancer pathology.
Early 2020: From Progastrin to hPG80
The protein is changing its name to put an end to the confusion that gives rise to misconceptions.
However, the cancer community does not acknowledge progastrin as a cancer target by itself due to its name, progastrin, which always brings us back to the past, progastrin as the precursor of gastrin.
Moreover, this misunderstanding is accentuated by the almost systematic confusion with a totally different peptide that is phonetically identical, the Pro-Gastrin Releasing Peptide (proGRP), which can be found in the scientific literature under several spellings (with or without a hyphen in progastrin or sometimes even under the name pre-progastrin releasing peptide...). Thus to date, more than half of the results concerning Progastrin on search engines concern this peptide and not the 80 amino acid molecule encoded by the GAST gene.
This is where the story of the hPG80 begins.
Also, in order to clearly distinguish:
intracellular progastrin, the precursor to gastrin,
extracellular progastrin (hPG80) which exerts oncogenic functions on tumor cells once released from the tumor cells,
pro-gastrin releasing peptide (proGRP),
we have been using the name hPG80 since the beginning of 2020 and the publication You et al. to unambiguously refer to the circulating Progastrin historically mentioned in the scientific literature under the single name Progastrin.
“h” means human, “PG” means Progastrin and “80” corresponds to the number of amino acids of this protein.
This is where the story of hPG80 starts: in order to clearly distinguish between progastrin as the precursor of gastrin and progastrin that exerts oncogenic functions on tumor cells once released from tumor cells, we proposed to rename progastrin once released from tumor cells as hPG80.
Today, hPG80 is the circulating progastrin, detected in the blood of patients with multiple cancers and exerting major oncogenic functions, the most relevant being that it is required for cancer stem cells survival.