{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:36:46Z","timestamp":1790073406980,"version":"4.0.1"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation of Korea (NRF) grant funded by the Korea government and Basic Science Research Capacity Enhancement Project through Korea Basic Science Institute (National research Facilities and Equipment Center) grant funded by the Mini","award":["2015M2B2B1068626 and 2019R1A6C1010003"],"award-info":[{"award-number":["2015M2B2B1068626 and 2019R1A6C1010003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Angiogenesis is critical for local tumor growth. This study aimed to develop a three-dimensional two-layer co-culture system to investigate effects of cancer cells on the growth of endothelial cells (ECs). Poly(\u03b5-caprolactone) (PCL) nanofibrous membranes were generated via electrospinning of PCL in chloroform (C-PCL-M) and chloroform and dimethylformamide (C\/DMF-PCL-M). We assembled a two-layer co-culture system using C-PCL-M and C\/DMF-PCL-M for EC growth in the upper layer with co-cultured cancer cells in the lower layer. In the absence of vascular endothelial growth factor (VEGF), growth of bEND.3 ECs decreased on C\/DMF-PCL-M but not on C-PCL-M with time. Growth of bEND.3 cells on C\/DMF-PCL-M was enhanced through co-culturing of CT26 cancer cells and enhanced growth of bEND.3 cells was abrogated with anti-VEGF antibodies and sorafenib. However, EA.hy926 ECs displayed steady growth and proliferation on C\/DMF-PCL-M, and their growth was not further increased through co-culturing of cancer cells. Moreover, chemical hypoxia in CT26 cancer cells upon treatment with CoCl2 enhanced the growth of co-cultured bEND.3 cells in the two-layer system. Thus, EC growth on the nanofibrous scaffold is dependent on the types of ECs and composition of nanofibers and this co-culture system can be used to analyze EC growth induced by cancer cells.<\/jats:p>","DOI":"10.3390\/ijms21114128","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T05:11:46Z","timestamp":1591765906000},"page":"4128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Co-Culturing of Endothelial and Cancer Cells in a Nanofibrous Scaffold-Based Two-Layer System"],"prefix":"10.3390","volume":"21","author":[{"given":"Ye-Seul","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Ajou University, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 16499, Korea"},{"name":"Immune Network Pioneer Research Center &amp; 3D Immune System Imaging Core Center, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-3169","authenticated-orcid":false,"given":"Jung-In","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9984-5668","authenticated-orcid":false,"given":"Perry Ayn Mayson A.","family":"Maza","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Young","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Ajou University, Suwon 16499, Korea"},{"name":"Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 16499, Korea"},{"name":"Immune Network Pioneer Research Center &amp; 3D Immune System Imaging Core Center, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1126\/science.2432664","article-title":"Angiogenic factors","volume":"235","author":"Folkman","year":"1987","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrd2115","article-title":"Angiogenesis: An organizing principle for drug discovery?","volume":"6","author":"Folkman","year":"2007","journal-title":"Nat. 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