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Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones
Published on: November 30, 2016
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Development of a Microphysiological System to Model Human Cancer Metastasis From the Colon to the Liver
Paula G Miller1, Emina Huang2, Robert Fisher2
1Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
Biotechnology and Bioengineering
|November 25, 2024
Summary
This study introduces a novel human model device that replicates the five stages of colon cancer metastasis to the liver. The system allows for in vitro assessment of metastatic potential, influenced by cancer cell source, clumping, glucose, and oxygen levels.
Area of Science:
- Oncology
- Biomedical Engineering
- Cell Biology
Background:
- Cancer metastasis is a complex, multi-step process responsible for the majority of cancer-related deaths.
- Current in vitro models often fail to replicate the entire metastatic cascade, limiting research into therapeutic strategies.
- Understanding the early stages of metastasis, particularly from colorectal cancer to the liver, is crucial for effective treatment.
Purpose of the Study:
- To develop and validate a novel in vitro human model that mimics the five key steps of the metastatic cascade.
- To enable the study of colorectal cancer (CRC) metastasis from the colon to the liver within a single, integrated device.
- To provide a platform for assessing metastatic capability in response to various biological and environmental factors.
Main Methods:
- A dual-organoid system comprising a colon mimic and a liver mimic, connected by a recirculating blood surrogate flow.
- The colon mimic utilizes normal colon epithelial organoids (NL) and human umbilical vein endothelial cells (HUVEC) with an air-liquid interface.
- The liver mimic incorporates human liver sinusoidal endothelial cells (HHSEC) and hepatic cells (HepG2 C3A) within Matrigel.
Main Results:
- The device successfully replicated all five steps of the metastatic cascade: invasion, intravasation, transport, extravasation, and colonization.
- Cell viability remained high (>85%) throughout the 5-day experimental period.
- Metastatic capability was shown to be dependent on cancer cell source, cell clumping, glucose concentration, and oxygen levels (hypoxia).
Conclusions:
- This novel in vitro system is the first to replicate all five steps of the metastatic cascade in a single human-based device.
- The model allows for rapid (5-day) in vitro assessment of metastatic potential and facilitates the study of interactions between metastatic steps.
- This platform offers a new tool to investigate factors influencing metastasis and to screen potential anti-metastatic therapies.
