STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts
The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing a favorable microenvironment that promotes can...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123000562 |
| _version_ | 1797862167106551808 |
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| author | Maria L. Ibba Giuseppe Ciccone Deborah Rotoli Gabriele Coppola Alfonso Fiorelli Silvia Catuogno Carla L. Esposito |
| author_facet | Maria L. Ibba Giuseppe Ciccone Deborah Rotoli Gabriele Coppola Alfonso Fiorelli Silvia Catuogno Carla L. Esposito |
| author_sort | Maria L. Ibba |
| collection | DOAJ |
| description | The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing a favorable microenvironment that promotes cancer progression. Therefore, the development of strategies inhibiting the interplay between CAFs and cancer cells is considered a winning approach for the development of effective anti-cancer drugs. Among other factors, the signal transducer and activator of transcription-3 (STAT3) has been reported as a key mediator of CAF oncogenic actions, representing a promising therapeutic target. Here, we applied an aptamer-based conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the platelet-derived growth factor receptor (PDGFR)β, to obtain STAT3-specific silencing and interfere with CAF pro-tumorigenic functions. We demonstrated that this molecule effectively delivers the STAT3 siRNA in NSCLC cells, and blocks CAF-induced cancer cell growth and migration and reduced spheroid dimension. In addition, we found that Gint4.T-STAT3 alters CAF phenotype, thus functioning as a double-acting molecule able to inhibit the entire tumor bulk. Our data provide a proof of principle for the targeting of CAF pro-tumor functions through an aptamer-based drug, and can open innovative horizons in NSCLC therapy. |
| first_indexed | 2024-04-09T22:14:51Z |
| format | Article |
| id | doaj.art-355f7b2b64c748fa9e32d04320a16a88 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-09T22:14:51Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-355f7b2b64c748fa9e32d04320a16a882023-03-23T04:35:29ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-06-0132111126STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblastsMaria L. Ibba0Giuseppe Ciccone1Deborah Rotoli2Gabriele Coppola3Alfonso Fiorelli4Silvia Catuogno5Carla L. Esposito6Institute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, Italy; Department of Precision Medicine, University of Campania ''L. Vanvitelli'', 80138 Naples, ItalyInstitute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, ItalyInstitute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, ItalyInstitute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, ''Federico II'' University of Naples, 80131 Naples, ItalyThoracic Surgery Unit, Università degli Studi della Campania ''Luigi Vanvitelli'', Naples, ItalyInstitute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, Italy; Corresponding author: S. Catuogno, Institute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, Italy.Institute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, Italy; Corresponding author: C.L. Esposito, Institute Experimental Endocrinology and Oncology ''Gaetano Salvatore'' (IEOS), National Research Council (CNR), 80145 Naples, Italy.The identification of new effective therapeutic options for non-small-cell lung cancer (NSCLC) represents a crucial challenge in oncology. Recent studies indicate that cancer-associated fibroblasts (CAFs) participate in tumor progression by establishing a favorable microenvironment that promotes cancer progression. Therefore, the development of strategies inhibiting the interplay between CAFs and cancer cells is considered a winning approach for the development of effective anti-cancer drugs. Among other factors, the signal transducer and activator of transcription-3 (STAT3) has been reported as a key mediator of CAF oncogenic actions, representing a promising therapeutic target. Here, we applied an aptamer-based conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the platelet-derived growth factor receptor (PDGFR)β, to obtain STAT3-specific silencing and interfere with CAF pro-tumorigenic functions. We demonstrated that this molecule effectively delivers the STAT3 siRNA in NSCLC cells, and blocks CAF-induced cancer cell growth and migration and reduced spheroid dimension. In addition, we found that Gint4.T-STAT3 alters CAF phenotype, thus functioning as a double-acting molecule able to inhibit the entire tumor bulk. Our data provide a proof of principle for the targeting of CAF pro-tumor functions through an aptamer-based drug, and can open innovative horizons in NSCLC therapy.http://www.sciencedirect.com/science/article/pii/S2162253123000562MT: Oligonucleotides: Therapies and ApplicationsaptamersiRNAchimerasNSCLCCAFs |
| spellingShingle | Maria L. Ibba Giuseppe Ciccone Deborah Rotoli Gabriele Coppola Alfonso Fiorelli Silvia Catuogno Carla L. Esposito STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications aptamer siRNA chimeras NSCLC CAFs |
| title | STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts |
| title_full | STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts |
| title_fullStr | STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts |
| title_full_unstemmed | STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts |
| title_short | STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts |
| title_sort | stat3 silencing by an aptamer based strategy hampers the crosstalk between nsclc cells and cancer associated fibroblasts |
| topic | MT: Oligonucleotides: Therapies and Applications aptamer siRNA chimeras NSCLC CAFs |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123000562 |
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