Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.

Journal Article (Journal Article)

Breast cancer (BC) is the most common malignancy in women. Particular subtypes with aggressive behavior are major contributors to poor outcomes. Triple-negative breast cancer (TNBC) is difficult to treat, pro-inflammatory, and highly metastatic. We demonstrate that TNBC cells express TLR9 and are responsive to TLR9 ligands, and treatment of TNBC cells with chemotherapy increases the release of nucleic-acid-containing damage-associated molecular patterns (NA DAMPs) in cell culture. Such culture-derived and breast cancer patient-derived NA DAMPs increase TLR9 activation and TNBC cell invasion in vitro . Notably, treatment with the polyamidoamine dendrimer generation 3.0 (PAMAM-G3) behaved as a nucleic acid scavenger (NAS) and significantly mitigates such effects. In mice that develop spontaneous BC induced by polyoma middle T oncoprotein (MMTV-PyMT), treatment with PAMAM-G3 significantly reduces lung metastasis. Thus, NAS treatment mitigates cancer-induced inflammation and metastasis and represents a novel therapeutic approach for combating breast cancer.

Full Text

Duke Authors

Cited Authors

  • Eteshola, EOU; Landa, K; Rempel, RE; Naqvi, IA; Hwang, ES; Nair, SK; Sullenger, BA

Published Date

  • December 2021

Published In

Volume / Issue

  • 26 /

Start / End Page

  • 1 - 10

PubMed ID

  • 34513289

Pubmed Central ID

  • PMC8408553

Electronic International Standard Serial Number (EISSN)

  • 2162-2531

International Standard Serial Number (ISSN)

  • 2162-2531

Digital Object Identifier (DOI)

  • 10.1016/j.omtn.2021.06.016

Language

  • eng