Details

Autor(en) / Beteiligte

• Eteshola, Elias O.U.
• Landa, Karenia
• Rempel, Rachel E.
• Naqvi, Ibtehaj A.
• Hwang, E. Shelley
• Nair, Smita K.
• Sullenger, Bruce A.

Titel

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

Ist Teil von

• Molecular therapy. Nucleic acids, 2021-12, Vol.26, p.1-10

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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. [Display omitted] Using a nucleic acid scavenger, Eteshola et al. present an innovative way to slow down metastasis following standard-of-care therapy in difficult-to-treat malignancies such as triple-negative breast cancer. By capturing tumor-derived nucleic acid-containing DAMPs in vitro and in a spontaneous transgenic murine model, this strategy lays the groundwork for improving the clinical management of cancer by adding an adjuvant that limits metastatic spread.