# A Robust Marine Collagen Peptide–Agarose 3D Culture System for In Vitro Modeling of Hepatocellular Carcinoma and Anti-Cancer Therapeutic Development

## TL;DR

Researchers developed a 3D culture system using marine collagen to model liver cancer, showing better tumor behavior and drug resistance compared to traditional methods.

## Contribution

A novel 3D in vitro model using marine collagen peptide-based hydrogel for hepatocellular carcinoma and cancer stem cell studies.

## Key findings

- MCP-B hydrogel spheroids showed enhanced tumor behaviors like proliferation, migration, and chemoresistance.
- Molecular analyses revealed upregulated genes linked to drug resistance, stemness, and cancer progression.
- The model retained liver-specific functions and extracellular matrix remodeling signatures.

## Abstract

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–mesenchymal 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.