DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
Rechercher
(titres de publication, de périodique et noms de colloque inclus)
2016-02-17 - Colloque/Présentation - poster - Anglais - 1 page(s)

Fanfone Deborah , Despretz Nadège, Stanicki Dimitri , Laurent Sophie , Muller Robert , Rorive Sandrine, Vander Elst Luce , Saussez Sven , Burtea Carmen , "Effects of novel galectin-1-targeted peptides on human cells in the context of a new and non-invasive thyroid cancer diagnosis" in Belgian Peptide Group Meeting, Bruxelles, Belgique, 2016

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243), Cancérologie (DI3349), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Anatomie et Biologie cellulaire (M112)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)

Abstract(s) :

(Anglais) Effects of novel galectin-1-targeted peptides on human cells in the context of a new and non-invasive thyroid cancer diagnosis D. Fanfone1, N. Despretz1, D. Stanicki1, S. Laurent1,2, R. N. Muller1,2, S. Rorive4, L. Vander Elst1,2, S. Saussez3, C. Burtea1 1 Department of General, Organic and Biomedical Chemistry, University of Mons 2 CMMI (Center for Microscopy and Molecular Imaging) 3 Laboratory of Anatomy and Cell Biology, University of Mons 4 Diapath, CMMI These last three decades, the worldwide incidence of the thyroid cancer, the most common endocrine malignancy, is still increasing1. Currently, 90% of surgeries performed on thyroid nodules reveal a benign phenotype2, suggesting a challenging diagnosis of patients who really need a surgery. Indeed current diagnosis approaches imply painful and useless thyroid surgeries. Thereby, we propose to develop a new and non-invasive diagnosis approach of papillary carcinoma, as the most frequent (~80%) malignant tumour of the thyroid. Galectin-1 (gal-1) has been targeted as a diagnostic tool for well-differentiated thyroid cancers. This small adhesion protein is expressed in muscles, neurons and embryonic tissues in non-pathologic conditions. Mostly secreted, it can also be found in the cytoplasm and the nucleus. It is involved in cellular adhesion, aggregation, migration and cell cycle regulation phenomena. Moreover, gal-1 has been found overexpressed in several cancers such as in thyroid cancer3. Actually, gal-1 is implied in tumour progression. Phage clones expressing peptides targeted to gal-1 were identified thanks to phage display technique. Three of them were selected based on their affinity and their corresponding peptides were synthesized: P1, P7 and P8. Subsequently, their cellular localization has been demonstrated by immunohistochemistry on human well-differentiated thyroid cancer slices. P1 and P7 showed a better specific affinity on histological sections. Moreover, they co-localized with gal-1 in TPC-1 cells (derived from papillary thyroid cancer) as demonstrated by immunofluorescence. Our interest was first focused on P1, which has been thereafter synthesized and conjugated to a MRI contrast agent (ultra-small particles of iron oxide, USPIO) in order to produce an MRI vectorized contrast agent able to diagnose non-invasively the papillary thyroid carcinoma. The binding of these vectorized nanoparticles has been validated on TPC-1 cells using a Perls’-DAB assay. USPIO conjugated with a non-specific peptide, used as a control, did not bind to these cells. Cytotoxicity assays have not revealed any significant toxicity of peptide 1 / USPIO-P1 in healthy hepatocytes, after 2 or 24 hours of incubation. Furthermore, the therapeutic context of papillary thyroid cancer was also approached. Indeed, the cell adhesion inhibitor potential of peptide 1 and of its scramble was studied on TPC-1 cells. When peptide 1 is incubated at 500 nM, around 25% of TPC-1 cells do not adhere anymore to galectin-1-coated wells, suggesting that the interaction between peptide 1 and gal-1 prevents TPC-1 cells adhesion to the substrate. Moreover, scramble peptide 1 does not induce any significant effect on cell adhesion. Peptide 1 coupled to USPIO seems to be a promising MRI contrast agent specific to gal-1 that could be useful for the thyroid cancer diagnosis. The vectorized contrast agent will be assessed on murine models of papillary thyroid cancer, subsequent to the evaluation of its biodistribution and pharmacokinetic parameters. As a therapeutic agent, peptide 1 significantly blocks the tumour cell adhesion to gal-1, suggesting an anti-metastatic effect. The cytotoxic and adhesion inhibition effects will be also studied for the P7 that will be also conjugated to iron nanoparticles. 1. Grant, C. S. Recurrence of papillary thyroid cancer after optimized surgery. Gland Surg. 4, 52–62 (2015). 2. Parangi, S. & Suh, H. The role of genetic markers in the evaluation and management of thyroid nodules. Surg. Clin. North Am. 94, 515–28 (2014). 3. Perillo, N. L. et al., L. G. Galectins: Versatile modulators of cell adhesion, cell proliferation, and cell death. J. Mol. Med. 76, 402–412 (1998).


Mots-clés :
  • (Anglais) galectin-1
  • (Anglais) thyroid cancer
  • (Anglais) peptides
  • (Anglais) phage display
  • (Anglais) molecular imaging