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| Status |
Public on Aug 31, 2018 |
| Title |
Intercellular transfer of small RNAs from astrocytes to lung tumor cells induces resistance to chemotherapy. |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Brain metastases are highly resistance to chemotherapy and have a poor prognosis for cure. Tumor cells are surrounded by activated astrocytes and exploit their cyto-protective properties for protection from apoptosis induced by chemotherapy. The mechanism by which astrocytes protect tumor cells is poorly understood. An important non-mutational mechanism of chemotherapy resistance is regulation of gene translation mediated by small non-coding RNAs (sRNAs), in particular, microRNAs (miRNAs). Here we studied the role of astrocytic sRNAs in promoting resistance of the human lung tumor PC14 cells to apoptosis induced by chemotherapy. To this end we compared the sRNA profile of human lung tumor cells that were cultured with or without astrocytes by miRNA microarray. The results show that sRNAs are transferred from astrocytes to PC14 cells in a contact-dependent manner. This transfer is fast and reached plateau already after six hours of co-culturing. Carbenoxolone, a broad-spectrum gap junction antagonist, inhibited the sRNAs transfer indicating that the sRNAs are transferred via gap-junction, maybe via survival pathways. Enforced expression of these sRNA in PC14 cells increased their resistance to the chemotherapy agent Taxol. In light of these results, we offer novel findings that may be clinically relevant to treatment development for brain metastases.
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| Overall design |
In the current study we focus on the potential transfer of smallRNAs from astrocytes to metastatic lung tumor cells and its outcome on the resistance of tumor cells to chemotherapy. Our experimental system comprised of co-culturing conditioned immortalized mice astrocytes (H-2K b-tsA58 mice, herein astrocytes) and human lung adenocarcinoma PC14 cell line.
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| Contributor(s) |
Menachem A, Makovski V, Bodner O, Pasmanik-Chor M, Stein R, Shomron N, Kloog Y |
| Citation(s) |
26871466 |
| Submission date |
Aug 31, 2015 |
| Last update date |
Dec 02, 2018 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
metsada@tauex.tau.ac.il
|
| Organization name |
Tel Aviv University
|
| Department |
Biology
|
| Lab |
Bioinformatics Unit
|
| Street address |
Ramat Aviv
|
| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
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| Platforms (1) |
| GPL14613 |
[miRNA-2] Affymetrix Multispecies miRNA-2 Array |
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| Samples (6)
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| GSM1864135 |
human lung tumor PC14 cells alone [D27_1] |
| GSM1864136 |
human lung tumor PC14 cells cultured (direct contact) with astrocytes [D28_3] |
| GSM1864137 |
human lung tumor PC14 cells cultured in transwell (TW) with astrocytes [D29_5] |
| GSM1864138 |
human lung tumor PC14 cells alone [D30_7] |
| GSM1864139 |
human lung tumor PC14 cells cultured (direct contact) with astrocytes [D31_9] |
| GSM1864140 |
human lung tumor PC14 cells cultured in transwell (TW) with astrocytes [D32_11] |
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| Relations |
| BioProject |
PRJNA294268 |
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