Romanian Biotechnological Letters Vol.24 , No. x, Copyright © 2019 University of Bucharest Printed in Romania. All rights reserved ORIGINAL PAPER 1 Expression of soluble biomarkers associated to cell proliferation, angiogenesis and oxidative stress in rats bearing Walker tumours Received for publication, January, 25, 2019 Accepted, March, 18, 2019 DANIELA GLAVAN 1 , CAMELIA MIA HOTNOG 2* , VALENTINA NEGOITA 1 , MIRELA MIHAILA 2 , LORELEI IRINA BRASOVEANU 2** , MARIA IULIANA GRUIA 1 , 1 “Prof. Dr. Alexandru Trestiorean” Institute of Oncology, Bucharest, Romania 2 “Stefan S. Nicolau” Institute of Virology, Center of Immunology, Bucharest, Romania *Principal co-author **Address for correspondence to: Lorelei I. Brasoveanu, e-mail: luli_brasoveanu@yahoo.com; “Stefan S. Nicolau” Institute of Virology, Center of Immunology, 285 Mihai Bravu Ave, S3, 030304, Bucharest, Romania, phone/ fax: +40-21-3241471 Abstract Carcinogenesis is a process that occurs in several stages where distinct changes occur, both at molecular and cellular levels, and involves three stages: tumour initiation, promotion, and progression. Proliferation is an important stage in the development and progression of cancer, and includes alterations of the expression and/or activity of the cell cycle related proteins, activation of multiple signal transduction pathways. Part of the survival strategy of these cells may be manifested by changes in cellular metabolism. After the onset of tumours, growth and metastasis can be sustained by overproduction of hormones (in hormone dependent cancers), by promoting angiogenesis, triggering autophagy. Tumours are biologically characterized in order to emphasize their proliferative, invasive and metastatic abilities. Aberrant glycosylation is often considered a "cancer fingerprint", playing a fundamental role in tumour development and progression. Resistance to treatment, escape from host immune system control, tumour invasion and angiogenesis, metastasis are closely related to aberrant sialilation of glycoproteins and glycolipids. The malignant phenotype is associated with the combined action of several exo-and endopeptidases, like cathepsin D. Oxidative stress refers to the imbalance between free radicals that form the pro-oxidant system and endogenous antioxidants, and the accumulation of reactive species in cancer cells plays an important role in the initiation and evolution of this disease. The aim of our study was the development of an experimental in vivo model, based on Walker 256 tumour bearing rats, for concomitant evaluation of the expression of soluble biomarkers associated with tumour progression, angiogenesis and oxidative stress. Since Walker 256 is a carcinosarcoma tumour, the implemented experimental model might be of great use in the oncology clinic to improve diagnostic, prognostic, metastatic risk assessment and treatment monitoring. Keywords: cathepsin D, sialic acid, oxidative stress, Walker 256 carcinosarcoma 1. Introduction Carcinogenesis is a process that occurs in several stages where distinct changes occur, both at molecular and cellular levels, and involves three stages: tumour initiation, promotion, and progression. Proliferation is an important stage in the development and progression of cancer, and includes alterations of the expression and / or activity of the cell cycle related proteins, activation of multiple signal transduction pathways (WEBER & al. [1]). Initial stages of tumour development are associated with a fibrinogenic response, and the development of a hypoxic environment that promotes the survival and proliferation of cancer stem cells. Part of the survival strategy of these cells may be manifested by changes in cellular metabolism (JEMAL & al. [2]). After the onset of tumours, growth and metastasis can be sustained by overproduction of hormones (in hormone dependent cancers), by promoting angiogenesis,