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2016-09-03 - 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 , "Study of novel galectin-1 targeted peptides in the context of a new and non-invasive papillary thyroid cancer diagnosis and evaluation of their potential inhibitor effect" in 39th annual meeting of the european thyroid association, Copenhague, Danemark, 2016

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), 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) Title: Study of novel galectin-1 targeted peptides in the context of a new and non-invasive papillary thyroid cancer diagnosis and evaluation of their potential inhibitor effect Abstract: Currently, the worldwide incidence of thyroid cancer, the most common endocrine malignancy, is still increasing. 90% of surgeries performed on nodules reveal a benign phenotype, suggesting a challenging diagnosis of patients who really need a surgery. Current diagnosis approaches imply painful and useless thyroid surgeries. Thereby, we propose to develop a new and non-invasive diagnosis approach by molecular MRI of papillary carcinoma (~80% of malignant tumours of the thyroid) by targeting galectin-1 (gal-1) with peptide functionalized imaging probes. Gal-1, a small protein involved in cellular adhesion, aggregation, migration and cell cycle regulation phenomena, has been found overexpressed in several cancers such as in thyroid cancer. Actually, gal-1 is implied in tumour progression and in metastasis development. Thanks to phage display technique, phage clones expressing gal-1-targeted peptides were identified. Based on their affinity, three of them were selected and their corresponding peptides synthesized: P1, P7 and P8. Their binding to gal-1 expressed by well-differentiated thyroid cancer sections has been validated by immunohistochemistry, P1 and P7 showing a better specific affinity. Immunofluorescence assays revealed colocalisation between the peptides and gal-1 in TPC-1 cells (derived from papillary thyroid cancer). P1 and P7 showed no toxicity on hepatocytes, allowing subsequent in vivo experiments. Each one of them was conjugated to ultra-small particles of iron oxide (USPIO-P1/P7) in order to obtain imaging probes able to diagnose non-invasively papillary thyroid carcinoma. The binding of vectorized nanoparticles to TPC-1 cells and their absence of toxicity have been validated. The two contrast agents will be assessed on murine models of papillary thyroid cancer, after evaluation of biodistribution and pharmacokinetic parameters. The therapeutic context of papillary thyroid cancer was also investigated. The potential of these two peptides to inhibit TPC-1 cell adhesion to gal-1 has been confirmed, suggesting thus an anti-metastatic effect.


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