Contents lists available at ScienceDirect Peptides journal homepage: www.elsevier.com/locate/peptides Changes in plasma levels of cholecystokinin, neurotensin, VIP and PYY in gastric and colorectal cancer – Preliminary results Aneta Lidia Zygulska a, ⁎ , Agata Furgala b , Jolanta Kaszuba-Zwoińska b , Krzysztof Krzemieniecki a,c , Krzysztof Gil b a Department of Oncology, Krakow University Hospital, 10 Sniadeckich St., 31-531, Krakow, Poland b Department of Pathophysiology, Jagiellonian University Medical College, 18 Czysta St., 31-121, Krakow, Poland c Department of Oncology, Jagiellonian University, 10 Sniadeckich St., 31-531, Krakow, Poland ARTICLE INFO Keywords: Gastrointestinal cancer Cholecystokinin (CCK) Neurotensin (NT) Vasoactive intestinal peptide (VIP) Peptide YY ABSTRACT Physiological roles of enterohormones such as secretion, absorption and digestion were supported by clinical data. Overexpression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) re- ceptors occur in gastrointestinal (GI) malignancies. The aim of the paper was to compare plasma levels of CCK, peptide YY (PYY), VIP and NT in patients with gastrointestinal malignancies and healthy controls. The study included 80 patients (37 men and 43 women) with GI malignancies (20 with gastric and 60 with colorectal cancers). Median age of the patients was 62.9 years (range: 40–85 years). Control group was comprised of 30 healthy persons with median age 59.8 years (range: 40–82 years). Fasting plasma concentrations of CKK, PYY, NT, and VIP were determined at rest, using ELISA kits for automated systems. Comparative analysis of en- terohormone levels in patients with various types of gastrointestinal malignancies demonstrated presence of some cancer-specific alterations. Patients with gastric cancers presented with lower plasma concentrations of CCK than healthy controls and individuals from colorectal cancers (p = 0.02). The highest plasma concentra- tions of neurotensin was found in colorectal cancer patients in comparison to gastric (p = 0.02). The plasma levels of VIP observed in gastric cancer group were lower than in colorectal cancer patients (p = 0.01). Patients with GI malignancies may present with tumor-specific alterations in plasma enterohormone levels. 1. Introduction Enterohormones stimulate proliferation of normal intestinal mucosa and control many physiological functions, such as endocrine secretion, absorption, digestion and motility of gastrointestinal tract. Patients with gastrointestinal malignancies were shown to present with over- expression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) receptors [1,2]. These findings may have im- plications for both cancer diagnostics and therapy. Cholecystokinin (CCK) is a gastrointestinal hormone structurally similar to gastrin, which stimulates secretion of pancreatic enzymes and gallbladder contractions [3–6]. CCK and gastrin are involved in control of many molecular processes, including proliferation, migration and apoptosis triggered by CCK1 and CCK2 receptors [5]. CCKA receptor is expressed on pancreatic acinar cells, whereas gastrin/CCKB receptor, recognizing sulphated and unsulphated gastrin, is found on gastric parietal cells, and gastrin/CCKC receptor on colorectal cancer cells [7]. Impaired release of CCK or mutations of the CCK receptors may con- tribute to pancreatic pathologies (e.g. acute/chronic pancreatitis), im- pairment of gastrointestinal motility (e.g. irritable bowel syndrome) and hypergastrinemia-related disorders (e.g. hyperplasia, carcinoid) [8]. CCK promotes development of gastrointestinal malignancies, acting via CCK1 and CCK2 receptors expressed by the tumor cells and via an autocrine/paracrine loop [4,7–10]. CCK receptors belong to the family with seven transmembrane segments. While CCKA receptor has greater affinity for sulfated CCK than for gastrin, the affinity of gastrin/ CCKB receptor for these two compounds is essentially the same [6]. Although the expression of CCK2 was observed in virtually all malig- nancies (gastrointestinal cancers, thyroid cancer, lung cancer, etc.), it was at a similar levels as in normal tissues [11–13]. Neurotensin (NT or NTS) is a 13-amino-acid neuropeptide expressed in the central and peripheral nervous system and in the digestive tract [14–18]. NT, found in enteroendocrine cells of the small intestine, regulates secretion and smooth muscle contraction [4,6]. As a hormone https://doi.org/10.1016/j.peptides.2019.170148 Received 13 April 2019; Received in revised form 29 August 2019; Accepted 2 September 2019 ⁎ Corresponding author at: Department of Oncology, Krakow University Hospital, 10 Sniadeckich St, 31-531, Krakow, Poland. E-mail addresses: zygulska@poczta.onet.pl (A.L. Zygulska), a.furgala@uj.edu.pl (A. Furgala), jkaszuba@cm-uj.krakow.pl (J. Kaszuba-Zwoińska), krzemieniecki@plusnet.pl (K. Krzemieniecki), mpgil@cyf-kr.edu.pl (K. Gil). Peptides 122 (2019) 170148 Available online 18 September 2019 0196-9781/ © 2019 Elsevier Inc. All rights reserved. T