The C-terminal flanking peptide of progastrin induces gastric cell apoptosis and stimulates colonic cell division in vivo

Marshall, Kathryn M.; Patel, Oneel; Bramante, Gianni; Laval, Marie; Yim, Mildred; Baldwin, Graham S.; Shulkes, Arthur

doi:10.1016/j.peptides.2013.05.009

Cited by 5 publications

(2 citation statements)

References 37 publications

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“…Enhanced proliferation of colonic cells in vivo by non-amidated G17-Gly, as well as a second immature PG-derived peptide, C-terminal flanking peptide (CTFP), was confirmed in mice model of liver metastasis. However, CTFP does not seem to influence xenograft growth or the incidence of LM [130]. In turn, in the case of mouse colon cancer stem/progenitor cells in vitro, an increased proliferation through PG/G protein-coupled receptor 56 (GPR56) and PG/CCK2R systems was reported [131].…”

Section: Gastrin/progastrinmentioning

confidence: 99%

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Kasprzak

Adamek

2020

IJMS

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Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.

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Section: Gastrin/progastrinmentioning

confidence: 99%

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Kasprzak

Adamek

2020

IJMS

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“…In this context it is worth noting that, in contrast, CFP has also been found to stimulate gastric apoptosis (Marshall et al . ). Moreover, progastrin expression by CCD133 + human primary colorectal cancer cells was vital for tumour growth (Ferrand et al .…”

Section: Introductionmentioning

confidence: 97%

Novel roles of gastrin

Dimaline

Varró

2014

The Journal of Physiology

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The existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as plasminogen activator inhibitors and matrix metalloproteinases that have important actions on extracellular matrix remodelling. These actions are, at least in part, effected by paracrine signalling pathways and make important contributions to maintaining functional integrity of the gastric epithelium. Recent studies also provide support for the idea that gastrin, in concert with other hormones, could potentially contribute a post-prandial incretin effect. We also review recent developments in the biology of other gastrin gene products, including the precursor progastrin, which causes proliferation of the colonic epithelium and in certain circumstances may induce cancer formation. Glycine-extended biosynthetic processing intermediates also have proliferative effects in colonic mucosa and in some oesophageal cancer cell lines. Whether these additional gene products exert their effects through the CCK2 receptor or a separate entity is currently a matter of debate.

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From amino acid sequence to bioactivity: The biomedical potential of antitumor peptides

et al. 2016

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Chemoprevention is the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. In this field, the use of antitumor peptides is of interest as, (i) these molecules are small in size, (ii) they show good cell diffusion and permeability, (iii) they affect one or more specific molecular pathways involved in carcinogenesis, and (iv) they are not usually genotoxic. We have checked the Web of Science Database (23/11/2015) in order to collect papers reporting on bioactive peptide (1691 registers), which was further filtered searching terms such as "antiproliferative," "antitumoral," or "apoptosis" among others. Works reporting the amino acid sequence of an antiproliferative peptide were kept (60 registers), and this was complemented with the peptides included in CancerPPD, an extensive resource for antiproliferative peptides and proteins. Peptides were grouped according to one of the following mechanism of action: inhibition of cell migration, inhibition of tumor angiogenesis, antioxidative mechanisms, inhibition of gene transcription/cell proliferation, induction of apoptosis, disorganization of tubulin structure, cytotoxicity, or unknown mechanisms. The main mechanisms of action of those antiproliferative peptides with known amino acid sequences are presented and finally, their potential clinical usefulness and future challenges on their application is discussed.

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The C-terminal flanking peptide of progastrin induces gastric cell apoptosis and stimulates colonic cell division in vivo

Cited by 5 publications

References 37 publications

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Novel roles of gastrin

From amino acid sequence to bioactivity: The biomedical potential of antitumor peptides

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