Author(s):
Nóbrega, Franklin Luzia ; Ferreira, Débora ; Martins, Ivone M. ; Maria Suarez-Diez ; Azeredo, Joana ; Rodrigues, L. R. ; Kluskens, Leon
Date: 2016
Persistent ID: http://hdl.handle.net/1822/43071
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/121028/PT
;
info:eu-repo/grantAgreement/FCT/COMPETE/121028/PT;
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/126270/PT
;
info:eu-repo/grantAgreement/FCT/COMPETE/126270/PT;
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F86462%2F2012/PT;
Subject(s): Claudin-low breast cancer; Phage display; MDA-MB-231; PRWAVSP; DTFNSFGRVRIE; Science & Technology
Description
Background: Claudin-low breast carcinoma represents 19% of all breast cancer cases and is characterized by an aggressive progression with metastatic nature and high rates of relapse. Due to a lack of known specific molecular biomarkers for this breast cancer subtype, there are no targeted therapies available, which results in the worst prognosis of all breast cancer subtypes. Hence, the identification of novel biomarkers for this type of breast cancer is highly important for early diagnosis and targeted therapy. Methods: In this work, we propose the identification of peptides for the specific recognition of MDA-MB-231, a cell line representative of claudin-low breast cancers, using phage display (both conventional panning and BRASIL). Binding assays were performed to select the most interesting peptides and bioinformatics approaches were applied to putatively identify the biomarkers to which these peptides bind. Results: Two peptides were selected using this methodology specifically targeting MDA-MB-231 cells, as demonstrated by a 4 to 9 log higher affinity as compared to control cells. The use of bioinformatics approaches provided relevant insights into possible cell surface targets for each peptide identified. Conclusions: The peptides herein identified may contribute to an earlier detection of claudin-low breast carcinomas and possibly to develop more individualized therapies.
This study was supported by the Portuguese Foundation for Science and Technology (FCT) and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects FCOMP-01–0124-FEDER021053 (PTDC/SAU-BMA/121028/2010), RECI/BBB-EBI/0179/2012 (FCOMP-01– 0124-FEDER-027462), the strategic funding of UID/BIO/04469/2013 unit, and the Projects “BioHealth – Biotechnology and Bioengineering approaches to improve health quality”, REF. NORTE-07–0124-FEDER-000027, and “BioInd – Biotechnology and Bioengineering for improved Industrial and Agro-Food processes”, REF. NORTE-07–0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. Franklin L. Nóbrega acknowledges FCT for the grant SFRH/BD/86462/2012.
