| Title |
Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, January 2016
|
| DOI | 10.1007/s10549-016-3683-5 |
| Pubmed ID | |
| Authors |
Johanna M. Tuomela, Jouko A. Sandholm, Mika Kaakinen, Katherine L. Hayden, Kirsi-Maria Haapasaari, Arja Jukkola-Vuorinen, Joonas H. Kauppila, Petri P. Lehenkari, Kevin W. Harris, David E. Graves, Katri S. Selander |
| Abstract |
Toll-like receptor 9 (TLR9) is a cellular DNA-receptor widely expressed in cancers. We previously showed that synthetic and self-derived DNA fragments induce TLR9-mediated breast cancer cell invasion in vitro. We investigated here the invasive effects of two nuclease-resistant DNA fragments, a 9-mer hairpin, and a G-quadruplex DNA based on the human telomere sequence, both having native phosphodiester backbone. Cellular uptake of DNAs was investigated with immunofluorescence, invasion was studied with Matrigel-assays, and mRNA and protein expression were studied with qPCR and Western blotting and protease activity with zymograms. TLR9 expression was suppressed through siRNA. Although both DNAs induced TLR9-mediated changes in pro-invasive mRNA expression, only the telomeric G-quadruplex DNA significantly increased cellular invasion. This was inhibited with GM6001 and aprotinin, suggesting MMP- and serine protease mediation. Furthermore, complexing with LL-37, a cathelicidin-peptide present in breast cancers, increased 9-mer hairpin and G-quadruplex DNA uptake into the cancer cells. However, DNA/LL-37 complexes decreased invasion, as compared with DNA-treatment alone. Invasion studies were conducted also with DNA fragments isolated from neoadjuvant chemotherapy-treated breast tumors. Also such DNA induced breast cancer cell invasion in vitro. As with the synthetic DNAs, this invasive effect was reduced by complexing the neoadjuvant tumor-derived DNAs with LL-37. We conclude that 9-mer hairpin and G-quadruplex DNA fragments are nuclease-resistant DNA structures that can act as invasion-inducing TLR9 ligands. Their cellular uptake and the invasive effects are regulated via LL-37. Although such structures may be present in chemotherapy-treated tumors, the clinical significance of this finding requires further studying. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 3% |
| Unknown | 29 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 30% |
| Student > Ph. D. Student | 7 | 23% |
| Student > Bachelor | 5 | 17% |
| Student > Master | 2 | 7% |
| Professor > Associate Professor | 1 | 3% |
| Other | 0 | 0% |
| Unknown | 6 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 23% |
| Medicine and Dentistry | 7 | 23% |
| Agricultural and Biological Sciences | 5 | 17% |
| Immunology and Microbiology | 2 | 7% |
| Neuroscience | 1 | 3% |
| Other | 0 | 0% |
| Unknown | 8 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 October 2018.
All research outputs
#15,354,849
of 22,840,638 outputs
Outputs from Breast Cancer Research and Treatment
#3,298
of 4,660 outputs
Outputs of similar age
#231,241
of 393,708 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#31
of 64 outputs
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