{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:36:06Z","timestamp":1778643366736,"version":"3.51.4"},"reference-count":144,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea government","award":["2022R1A5A2027161"],"award-info":[{"award-number":["2022R1A5A2027161"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The development of physiologically relevant three-dimensional (3D) culture systems is essential for modeling tumor complexity and improving the translational impact of cancer research. We established a 3D in vitro model of human hepatocellular carcinoma (HCC) using a marine collagen peptide-based (MCP-B) biomimetic hydrogel scaffold optimized for multicellular spheroid growth. Compared with conventional two-dimensional (2D) cultures, the MCP-B hydrogel more accurately recapitulated native tumor biology while offering simplicity, reproducibility, bioactivity, and cost efficiency. HCC cells cultured in MCP-B hydrogel displayed tumor-associated behaviors, including enhanced proliferation, colony formation, migration, invasion, and chemoresistance, and enriched cancer stem cell (CSC) populations. Molecular analyses revealed upregulated expression of genes associated with multidrug resistance; stemness regulation and markers; epithelial\u2013mesenchymal transition (EMT) transcription factors, markers, and effectors; growth factors and their receptors; and cancer progression. The spheroids also retained liver-specific functions, suppressed apoptotic signaling, and exhibited extracellular matrix remodeling signatures. Collectively, these findings demonstrate that the 3D HCC model using MCP-B hydrogel recapitulates key hallmarks of tumor biology and provides a robust, physiologically relevant platform for mechanistic studies of HCC and CSC biology. This model further holds translational value for preclinical drug screening and the development of novel anti-HCC and anti-CSC therapeutics.<\/jats:p>","DOI":"10.3390\/md23100386","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T12:59:46Z","timestamp":1759150786000},"page":"386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Robust Marine Collagen Peptide\u2013Agarose 3D Culture System for In Vitro Modeling of Hepatocellular Carcinoma and Anti-Cancer Therapeutic Development"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1980-1871","authenticated-orcid":false,"given":"Lata","family":"Rajbongshi","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Eui","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su-Rin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-5742","authenticated-orcid":false,"given":"Seon-Yeong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuna","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Mi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"},{"name":"Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sae-Ock","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6693-0003","authenticated-orcid":false,"given":"Byoung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Biomedical Convergence Engineering, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6828-401X","authenticated-orcid":false,"given":"Dongjun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine, Pusan National University College of Medicine, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6449-0761","authenticated-orcid":false,"given":"Sik","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea"},{"name":"Immune Reconstitution Research Center of Medical Research Institute, Pusan National University College of Medicine, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41392-024-02075-w","article-title":"Hepatocellular carcinoma: Signaling pathways and therapeutic advances","volume":"10","author":"Zheng","year":"2025","journal-title":"Signal Transduct. 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