Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its receptor PROKR2 are associated to human colorectal cancer progression and peritoneal carcinomatosis

Article type: Research Article

Authors: Benlahfid, Mohammed^{a; *} | Traboulsi, Wael^{b; c; d} | Sergent, Frederic^{b; c; d} | Benharouga, Mohamed^{c; d; e} | Elhattabi, Khalid^{a; f} | Erguibi, Driss^{a; f} | Karkouri, Mehdi^f | Elattar, Hicham^g | Fadil, Abdelaziz^f | Fahmi, Yassine^f | Aboussaouira, Touria^{a; 1} | Alfaidy, Nadia^{b; c; d; 1}

Affiliations: [a] Laboratory of Scientific and Clinical Researches in Cancerous Pathologies, Faculty of Medicine and Pharmacy, University Hassan II of Casablanca, Casablanca, Morocco | [b] Institut National de la Santé et de la Recherche Médicale U1036, Grenoble, France | [c] University Grenoble-Alpes, Grenoble, France | [d] Commissariat à l’Energie Atomique et aux Energies Alternatives, Biosciences and Biotechnology Institute of Grenoble, Grenoble, France | [e] Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France | [f] Ibn Rochd University Hospital of Casablanca, University Hassan II of Casablanca, Casablanca, Morocco | [g] Laboratory of anatomopathology Moulay Driss 1e⁢r, Casablanca, Morocco

Correspondence: [*] Corresponding author: Mohammed Benlahfid, University Hassan II of Casablanca, Faculty of Medicine and Pharmacy, B.P.5696. Casablanca, Morocco. E-mail: benlahfid.med@gmail.com.

Note: [1] Equal contribution.

Abstract: BACKGROUND: The highest risk factor for mortality among malignant tumors is metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor which biological activity is mediated via two G protein-coupled receptors, prokineticin receptor1 (PROKR1) and PROKR2. Recent studies suggested that EG-VEGF expression is deregulated in multiple cancers including colorectal cancer (CRC). METHODS: Using distinctive CRC and peritoneal carcinomatosis (PC) cohorts and a corresponding control cohort, we determined the circulating levels of EG-VEGF and its in situ expression, and that of its related receptors. RESULTS: Circulating EG-VEGF levels were significantly increased in patients with metastatic PC compared to CRC and control patients (p< 0.05). Furthermore, according to clinicopathologic examinations, local EG-VEGF expression correlated with higher tumor and nodal stages (p< 0.001) of CRC. EG-VEGF and PROKR2 were highly expressed in colorectal primary lesions compared to positive controls. PROKR1 expression was lower and did not change in tumor specimens. Also, EG-VEGF and its receptor PROKR2 were differentially expressed in the colorectal primary lesions and in the control groups. CONCLUSION: Altogether these findings suggest that EG-VEGF/receptors system might be an important actor in the CRC progression into PC and might be involved in the ability of tumor cells to invade other organs. Circulating EG-VEGF could be proposed as a prognostic marker in human CRC and its progression into PC.

Keywords: Prokineticin, colorectal cancer, peritoneal carcinomatosis, EG-VEGF

DOI: 10.3233/CBM-170499

Journal: Cancer Biomarkers, vol. 21, no. 2, pp. 345-354, 2018