Deregulation of sialidases in human normal and tumor tissues

Article type: Research Article

Authors: Forcella, Matilde^a | Mozzi, Alessandra^a | Stefanini, Federico M.^b | Riva, Alice^c | Epistolio, Samantha^c | Molinari, Francesca^c | Merlo, Elisabetta^c | Monti, Eugenio^{d; *} | Fusi, Paola^{a; 1} | Frattini, Milo^{c; 1; *}

Affiliations: [a] Department of Biotechnologies and Biosciences, University of Milano-Bicocca, Milan, Italy | [b] Department of Statistics, Computer Science, Applications, University of Florence, Florence, Italy | [c] Institute of Pathology, Locarno, Switzerland | [d] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

Correspondence: [*] Corresponding authors: Eugenio Monti, Section of Biotechnology, Department of Molecular and Translational Medicine (DMTM), University of Brescia, Viale Europa 11, Brescia 25123, Italy. Tel.: +39 030 3717560; Fax: +39 030 3701157; E-mail: eugenio.monti@unibs.itorMiloFrattini,LaboratoryofMolecularPathology,InstituteofPathology,ViainSelva,24,LocarnoCH-6600,Switzerland.Tel.:+41918160805;Fax:+41918160719;E-mail:milo.frattini@ti.ch.

Note: [1] Paola Fusi and Milo Frattini are Joint Senior Authors.

Abstract: BACKGROUND: Aberrant sialylation is a characteristic feature associated with cancer. The four types of mammalian sialidases identified to date have been shown to behave in different manners during carcinogenesis. While NEU1, NEU2 and NEU4 have been observed to oppose malignant phenotypes, the membrane-bound sialidase NEU3 was revealed to promote cancer progression. OBJECTIVES: With the aim of improving the knowledge about sialidases deregulation in various cancer types, we investigated the amount of NEU1, NEU3 and NEU4 transcripts in paired normal and tumor tissues from 170 patients with 11 cancer types. METHODS: mRNA was extracted from patients’ tissue specimens and retrotranscribed into cDNA, which was quantified by Real-Time PCR. RESULTS: We found NEU1 and NEU3 to be up regulated, while NEU4 was down regulated in most cancer types. In particular, colorectal cancer tissues showed the highest increase in NEU3 expression. Both NEU1 and NEU3 showed a strong up-regulation in ovarian cancer. CONCLUSIONS: Our data show that human sialidases are expressed at different levels in healthy tissues and are strongly deregulated in tumors. Moreover, sialidases expression in our European cohort showed significant differences from Asian populations. Some of these peculiar features open potential applications of sialidases in cancer diagnosis and therapy.

Keywords: Sialome, sialidase expression, cancer progression, diagnosis and therapy

DOI: 10.3233/CBM-170548

Journal: Cancer Biomarkers, vol. 21, no. 3, pp. 591-601, 2018