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| Status |
Public on Nov 06, 2021 |
| Title |
Gene expression profiling of TNBC cells engineered to knock-down or overexpress PTX3 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The pattern recognition receptor long pentraxin-3 (PTX3) plays conflicting roles in cancer by acting as an oncosuppressor or as a pro-tumor mediator depending on tumor context. Triple negative breast cancer (TNBC) represents the most aggressive histotype of breast cancer, characterized by the lack of efficacious therapeutic targets/approaches and poor prognosis. In this study, in silico data and experimental evidences indicate that PTX3 is produced by tumor parenchyma in TNBC and that its expression levels correlate with tumor stage. On this basis, the impact of PTX3 silencing or its overexpression on the tumorigenic potential of TNBC cell lines was analyzed. Gene expression and in vitro results demonstrate that high levels of PTX3 expression confer a high aggressive/proliferative phenotype, fosters stem-like features, and rewires the energy metabolism in TNBC cells. This results in a more tumorigenic potential in vivo when TNBC cells are grafted in immune-compromised and syngeneic animals. Mechanistically, our data reveal a strong positive correlation between PTX3 expression and the antitumor activity of Toll-like receptor 4 (TLR4) inhibition in TBNC, demonstrating for the first time that PTX3-driven TNBC aggressiveness is due to PTX3-mediated activation of TLR4 signaling. Altogether, these data shed light on the role of tumor-produced PTX3 in TNBC and uncover the importance of the PTX3/TLR4 pathway for therapeutic and prognostic exploitation in TNBC.
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| Overall design |
MDA-MB 231 cells were infected with lentiviral vector containing short-hairpin RNA (shRNA) targeting human PTX3 (TRCN0000436981) (MDA-MB 231 shPTX3) or a non-targeting/control sequence (SHC002V, Merck) (MDA-MB 231 shNT); MDA-MB 468 cells were infected with a pLentiPGK-Puro (Addgene Plasmid #19070) lentiviral vector harbouring (MDA-MB 468 PTX3) or not (MDA-MB 468 mock) the full length human PTX3 cDNA (GenBank accession n° X63613)
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| Contributor(s) |
Giacomini A, Ronca R |
| Citation(s) |
37749607 |
| |
| Submission date |
Nov 05, 2021 |
| Last update date |
Oct 03, 2023 |
| Contact name |
Roberto Ronca |
| E-mail(s) |
roberto.ronca@unibs.it
|
| Organization name |
University of brescia
|
| Street address |
viale Europa 11
|
| City |
Brescia |
| ZIP/Postal code |
25123 |
| Country |
Italy |
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| Platforms (1) |
| GPL17692 |
[HuGene-2_1-st] Affymetrix Human Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA778246 |
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