Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment
Experiments were performed in a modified microfluidic platform recapitulating part of the in vivo tumor microenvironment by co-culturing carcinoma cell aggregates embedded in a three-dimensional (3D) collagen scaffold with human umbilical vein endothelial cells (HUVECs). HUVECs were seeded in one ch...
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| Format: | Article |
| Language: | en_US |
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Impact Journals/National Center for Biotechnology Information (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/99699 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1811097512623210496 |
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| author | Bai, Jing Tu, Ting-Yuan Kim, Choong Thiery, Jean Paul Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Bai, Jing Tu, Ting-Yuan Kim, Choong Thiery, Jean Paul Kamm, Roger Dale |
| author_sort | Bai, Jing |
| collection | MIT |
| description | Experiments were performed in a modified microfluidic platform recapitulating part of the in vivo tumor microenvironment by co-culturing carcinoma cell aggregates embedded in a three-dimensional (3D) collagen scaffold with human umbilical vein endothelial cells (HUVECs). HUVECs were seeded in one channel of the device to initiate vessel-like structures in vitro prior to introducing the aggregates. The lung adenocarcinoma cell line A549 and the bladder carcinoma cell line T24 were tested. Dose-response assays of four drugs known to interfere with Epithelial Mesenchymal Transition (EMT) signaling pathways were quantified using relative dispersion as a metric of EMT progression. The presence of HUVECs in one channel induces cell dispersal in A549 which then can be inhibited by each of the four drugs. Complete inhibition of T24 aggregate dispersal, however, is not achieved with any single agent, although partial inhibition was observed with 10 μM of the Src inhibitor, AZD-0530. Almost complete inhibition of T24 dispersal in monoculture was achieved only when the four drugs were added in combination, each at 10 μM concentration. Coculture of T24 with HUVECs forfeits the almost-complete inhibition. The enhanced dispersal observed in the presence of HUVECs is a consequence of secretion of growth factors, including HGF and FGF-2, by endothelial cells. This 3D microfluidic co-culture platform provides an in vivo-like surrogate for anti-invasive and anti-metastatic drug screening. It will be particularly useful for defining combination therapies for aggressive tumors such as invasive bladder carcinoma. |
| first_indexed | 2024-09-23T17:00:33Z |
| format | Article |
| id | mit-1721.1/99699 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:00:33Z |
| publishDate | 2015 |
| publisher | Impact Journals/National Center for Biotechnology Information (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/996992022-10-03T09:45:57Z Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment Bai, Jing Tu, Ting-Yuan Kim, Choong Thiery, Jean Paul Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Bai, Jing Kamm, Roger Dale Experiments were performed in a modified microfluidic platform recapitulating part of the in vivo tumor microenvironment by co-culturing carcinoma cell aggregates embedded in a three-dimensional (3D) collagen scaffold with human umbilical vein endothelial cells (HUVECs). HUVECs were seeded in one channel of the device to initiate vessel-like structures in vitro prior to introducing the aggregates. The lung adenocarcinoma cell line A549 and the bladder carcinoma cell line T24 were tested. Dose-response assays of four drugs known to interfere with Epithelial Mesenchymal Transition (EMT) signaling pathways were quantified using relative dispersion as a metric of EMT progression. The presence of HUVECs in one channel induces cell dispersal in A549 which then can be inhibited by each of the four drugs. Complete inhibition of T24 aggregate dispersal, however, is not achieved with any single agent, although partial inhibition was observed with 10 μM of the Src inhibitor, AZD-0530. Almost complete inhibition of T24 dispersal in monoculture was achieved only when the four drugs were added in combination, each at 10 μM concentration. Coculture of T24 with HUVECs forfeits the almost-complete inhibition. The enhanced dispersal observed in the presence of HUVECs is a consequence of secretion of growth factors, including HGF and FGF-2, by endothelial cells. This 3D microfluidic co-culture platform provides an in vivo-like surrogate for anti-invasive and anti-metastatic drug screening. It will be particularly useful for defining combination therapies for aggressive tumors such as invasive bladder carcinoma. Singapore-MIT Alliance for Research and Technology National University of Singapore. Cancer Science Institute National Cancer Institute (U.S.) (Grant R33 CA174550-01) 2015-11-04T13:25:41Z 2015-11-04T13:25:41Z 2015-10 2015-03 Article http://purl.org/eprint/type/JournalArticle 1949-2553 http://hdl.handle.net/1721.1/99699 Bai, Jing, Ting-Yuan Tu, Choong Kim, Jean Paul Thiery, and Roger D. Kamm. “Identification of Drugs as Single Agents or in Combination to Prevent Carcinoma Dissemination in a Microfluidic 3D Environment.” Oncotarget (November 2, 2015). https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.18632/oncotarget.5464 Oncotarget Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Impact Journals/National Center for Biotechnology Information (U.S.) Impact Journals/National Center for Biotechnology Information (U.S.) |
| spellingShingle | Bai, Jing Tu, Ting-Yuan Kim, Choong Thiery, Jean Paul Kamm, Roger Dale Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment |
| title | Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment |
| title_full | Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment |
| title_fullStr | Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment |
| title_full_unstemmed | Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment |
| title_short | Identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3D environment |
| title_sort | identification of drugs as single agents or in combination to prevent carcinoma dissemination in a microfluidic 3d environment |
| url | http://hdl.handle.net/1721.1/99699 https://orcid.org/0000-0002-7232-304X |
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