| Autor: |
Paola Pellegrini, Stig Linder, Slavica Brnjic, Katja Pokrovskaja Tamm, Hanif Rassoolzadeh, Dan Grandér, Sofi Forsberg, Rolf Larsson, Elin Edsbäcker, Elise G. Holvey-Bates, Angelo De Milito, George Stark Stark, Iryna Kolosenko, HyeonJoo Cheon, Per Johnsson, Mårten Fryknäs |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
International Journal of Cancer. 136:E51-E61 |
| ISSN: |
0020-7136 |
| DOI: |
10.1002/ijc.29161 |
| Popis: |
The mechanism of multicellular drug resistance, defined as the reduced efficacy of chemotherapeutic drugs in solid tumors is incompletely understood. Here we report that colon carcinoma cells cultured as 3D microtissues (spheroids) display dramatic increases in the expression of a subset of type I interferon-(IFN)-stimulated genes (ISGs). A similar gene signature was associated previously with resistance to radiation and chemotherapy, prompting us to examine the underlying biological mechanisms. Analysis of spheroids formed by different tumor cell lines and studies using knock-down of gene expression showed that cell crowding leads to the induction of IFN regulatory factor-9 (IRF9) which together with STAT2 and independently of IFNs, is necessary for ISG upregulation. Increased expression of IRF9 alone was sufficient to induce the ISG subset in monolayer cells and to confer increased resistance to clinically used cytotoxic drugs. Our data reveal a novel mechanism of regulation of a subset of ISGs, leading to drug resistance in solid tumors. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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