Development, Characterization, and In Vivo Evaluation of a Novel Aptamer (Anti-MUC1/Y) for Breast Cancer Therapy.

Huma Khan,Ralph Santos-Oliveira,Sotiris Missailidis,Sofia Nascimento Dos Santos,Vaidehi Makwana,Carlos Eduardo Bonacossa De Almeida

doi:10.3390/pharmaceutics13081239

Abstract

MUC1, the transmembrane glycoprotein Mucin 1, is usually found to be overexpressed in a variety of epithelial cancers playing an important role in disease progression. MUC1 isoforms such as MUC1/Y, which lacks the entire variable number of tandem repeat region, are involved in oncogenic processes by enhancing tumour initiation. MUC1/Y is therefore considered a promising target for the identification and treatment of epithelial cancers; but so far, the precise role of MUC1/Y remains to be elucidated. In this work, we developed and identified a DNA aptamer that specifically recognizes the splice variant MUC1/Y for the first time. The DNA aptamer could bind to a wide variety of human cancer cells, and treatment of MUC1/Y positive cells resulted in reduced growth in vitro. Moreover, MUC1/Y aptamer inhibited the tumour growth of breast cancer cells in vivo. The present study highlights the importance of targeting MUC1/Y for cancer treatment and unravels the suitability of a DNA aptamer to act as a new therapeutic tool.

Highlights

Introduction published maps and institutional affilThe epithelial mucin 1 (MUC1) is a functional protein with important roles in the survival of cells
Since the MUC1/Y splice variant is a transmembrane protein, the full protein cannot be used in the selection procedure due to the complexities involved in its isolation and purification
Sequencing the aptamers from the 3 M NaSCN elution, we observed sequence consensus with the identification of three potentially high binding aptamers (S11, S51, and S75, Table 1), which were present in the 40 sequences obtained from the initial single-round selection protocols, both against the 10mer and 20mer peptides; this indicated that these three aptamers bind to both the 10mer and 20mer peptides of MUC1/Y

Summary

Introduction

The epithelial mucin 1 (MUC1) is a functional protein with important roles in the survival of cells. MUC1 is distinctly associated with many malignancies, where several original characteristics of the protein are lost. As opposed to the typical expression, which is restricted to the apical surface of normal epithelial cells, MUC1 is found to be overexpressed in many adenocarcinomas, such as those of the breast, lung, ovary, pancreas, prostate, and numerous other epithelial organs. MUC1 displays many different features on tumour cells compared with the native protein, such as significantly reduced glycosylation due to the lessening number of tandem repeats present in the extracellular domain, combined with the extra addition of sialic acids, which distort the cellular adhesion properties on malignant cells [2].

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Results

Conclusion