Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

49 Scopus Citations
View graph of relations

Author(s)

  • Adi Gilboa-Geffen
  • Peter Hamar
  • Lee Adam Wheeler
  • Radiana Trifonova
  • Fabio Petrocca
  • Anders Wittrup
  • Judy Lieberman

Detail(s)

Original languageEnglish
Pages (from-to)2279-2291
Journal / PublicationMolecular Cancer Therapeutics
Volume14
Issue number10
Publication statusPublished - 1 Oct 2015
Externally publishedYes

Abstract

Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (TIC, also known as cancer stem cells). Here, we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knock down gene expression in EpCAM+ cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosphere formation (in vitro TIC assays) and tumor initiation by EpCAM+ luminal and basal-A triple-negative breast cancer (TNBC) cell lines, but not EpCAM+ mesenchymal basal-B TNBCs, in nude mice. Subcutaneously administered EpCAM-AsiCs concentrate in EpCAM+ Her2+ and TNBC tumors and suppress their growth. Thus, EpCAM-AsiCs provide an attractive approach for treating epithelial cancer.

Citation Format(s)

Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells. / Gilboa-Geffen, Adi; Hamar, Peter; Le, Minh T.N.; Wheeler, Lee Adam; Trifonova, Radiana; Petrocca, Fabio; Wittrup, Anders; Lieberman, Judy.

In: Molecular Cancer Therapeutics, Vol. 14, No. 10, 01.10.2015, p. 2279-2291.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review