Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer
The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although signifi...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-07-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23000439 |
| _version_ | 1797861094599950336 |
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| author | Menekse Ermis Natashya Falcone Natan Roberto de Barros Marvin Mecwan Reihaneh Haghniaz Auveen Choroomi Mahsa Monirizad Yeji Lee Jihyeon Song Hyun-Jong Cho Yangzhi Zhu Heemin Kang Mehmet R. Dokmeci Ali Khademhosseini Junmin Lee Han-Jun Kim |
| author_facet | Menekse Ermis Natashya Falcone Natan Roberto de Barros Marvin Mecwan Reihaneh Haghniaz Auveen Choroomi Mahsa Monirizad Yeji Lee Jihyeon Song Hyun-Jong Cho Yangzhi Zhu Heemin Kang Mehmet R. Dokmeci Ali Khademhosseini Junmin Lee Han-Jun Kim |
| author_sort | Menekse Ermis |
| collection | DOAJ |
| description | The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-β1 (TGF-β1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-β1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications. |
| first_indexed | 2024-04-09T21:56:32Z |
| format | Article |
| id | doaj.art-85ff2abeeaca4f4f9bcda00ecc219473 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-09T21:56:32Z |
| publishDate | 2023-07-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-85ff2abeeaca4f4f9bcda00ecc2194732023-03-24T04:23:11ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-07-0125360373Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancerMenekse Ermis0Natashya Falcone1Natan Roberto de Barros2Marvin Mecwan3Reihaneh Haghniaz4Auveen Choroomi5Mahsa Monirizad6Yeji Lee7Jihyeon Song8Hyun-Jong Cho9Yangzhi Zhu10Heemin Kang11Mehmet R. Dokmeci12Ali Khademhosseini13Junmin Lee14Han-Jun Kim15Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USADepartment of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of KoreaDepartment of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of KoreaCollege of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of KoreaTerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USADepartment of Materials Science and Engineering, Korea University, Seoul, 02841, Republic of KoreaTerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USATerasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USA; Corresponding author. Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USA.Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of Korea; Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Incheon 21983, Republic of Korea; Corresponding author. Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of Korea.Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024, USA; College of Pharmacy, Korea University, Sejong, 30019, Republic of Korea; Corresponding author. College of Pharmacy, Korea University, Sejong, 30019, Republic of Korea.The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-β1 (TGF-β1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-β1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.http://www.sciencedirect.com/science/article/pii/S2452199X23000439Pancreatic cancerDesmoplasiaFibrosisExtracellular matrixTumor microenvironment |
| spellingShingle | Menekse Ermis Natashya Falcone Natan Roberto de Barros Marvin Mecwan Reihaneh Haghniaz Auveen Choroomi Mahsa Monirizad Yeji Lee Jihyeon Song Hyun-Jong Cho Yangzhi Zhu Heemin Kang Mehmet R. Dokmeci Ali Khademhosseini Junmin Lee Han-Jun Kim Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer Bioactive Materials Pancreatic cancer Desmoplasia Fibrosis Extracellular matrix Tumor microenvironment |
| title | Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer |
| title_full | Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer |
| title_fullStr | Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer |
| title_full_unstemmed | Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer |
| title_short | Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer |
| title_sort | tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer |
| topic | Pancreatic cancer Desmoplasia Fibrosis Extracellular matrix Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23000439 |
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