Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread

Strelez, Carly; Chilakala, Sujatha; Ghaffarian, Kimya; Lau, Roy; Spiller, Erin; Ung, Nolan; Hixon, Danielle; Yoon, Ah Young; Sun, Ren; Lenz, Heinz‐Josef; Katz, Jonathan E.; Mumenthaler, Shannon M.

doi:10.1016/j.isci.2021.102509

Cited by 39 publications

(58 citation statements)

References 78 publications

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“…CRC cell seeding is performed 40–48 h after the Intestine-chips have been connected to flow ( Figure 2 ). Prepare Intestine-chip with appropriate extracellular matrix (ECM) (details are available in the materials and equipment section), intestinal epithelial cells (Caco2 C2BBe1) and HUVECs as detailed in ( Kim et al., 2012 ; Strelez et al . , 2021 ).…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…A previously described Intestine-chip, with Caco2 C2BBe1 cells intended to model non-diseased gut epithelium located in the top epithelial channel and human umbilical vein endothelial cells (HUVECs) in the bottom endothelial channel, includes fluid flow through the channels and cyclic, mechanical stretching motions to recreate peristalsis present in the gut ( Jalili-Firoozinezhad et al., 2018 ; Kim et al., 2012 , 2016 ). Here, we expand upon this model to create a colorectal cancer (CRC) on chip (CRC-on-chip) by integrating CRC cell lines into an environment that more closely emulates human CRC ( Figure 1 ) ( Strelez et al., 2021 ). We describe a multiplexed analysis of chip effluent and on-chip imaging to assess tumor cell behavior, with a primary focus on invasion and early metastatic spread.…”

Section: Before You Beginmentioning

confidence: 99%

“…Tests were conducted to ensure the formation of an intact barrier of the Intestine-chips and the CRC-chips ( Strelez et al . , 2021 ) but transepithelial/transendothelial electrical resistance (TEER) measurements were not taken.…”

Section: Limitationsmentioning

confidence: 99%

“…This protocol provides step-by-step details for tumor cell seeding to create a CRC-on-chip model, chip effluent collection and analysis, and on-chip imaging to monitor tumor cell invasion within a more physiologically relevant microenvironment. For complete details on the use and execution of this protocol, please refer to Strelez et al. (2021) .…”

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confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Strelez et al. (2021) .…”

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confidence: 99%

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Multiplexed imaging and effluent analysis to monitor cancer cell intravasation using a colorectal cancer-on-chip

2021

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Summary Despite colorectal cancer’s (CRC) prevalence, its progression is not well understood. The microfluidic organ-on-chip (OOC) model described herein recreates the epithelial-endothelial tissue-tissue interface, fluid flow, and mechanical forces that exist in vivo , making it an attractive model to understand and ultimately disrupt CRC intravasation. This protocol provides step-by-step details for tumor cell seeding to create a CRC-on-chip model, chip effluent collection and analysis, and on-chip imaging to monitor tumor cell invasion within a more physiologically relevant microenvironment. For complete details on the use and execution of this protocol, please refer to Strelez et al. (2021) .

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Section: Step-by-step Methods Detailsmentioning

confidence: 99%

Section: Before You Beginmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Strelez et al. (2021) .…”

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confidence: 99%

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Multiplexed imaging and effluent analysis to monitor cancer cell intravasation using a colorectal cancer-on-chip

2021

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Cancer Metastasis‐on‐a‐Chip for Modeling Metastatic Cascade and Drug Screening

Brooks,

Zhang,

Chen

et al. 2024

Adv Healthcare Materials

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Microfluidic chips are valuable tools for studying intricate cellular and cell‐microenvironment interactions. Traditional in vitro cancer models lack accuracy in mimicking the complexities of in vivo tumor microenvironment. However, cancer‐metastasis‐on‐a‐chip (CMoC) models combine the advantages of three dimensional (3D) cultures and microfluidic technology, serving as powerful platforms for exploring cancer mechanisms and facilitating drug screening. These chips are able to compartmentalize the metastatic cascade, deepening our understanding of its underlying mechanisms. This article provides an overview of current CMoC models, focusing on distinctive models that simulate invasion, intravasation, circulation, extravasation, and colonization, and their applications in drug screening. Furthermore, we discuss challenges faced by CMoC and microfluidic technologies, while exploring promising future directions in cancer research. The ongoing development and integration of these models into cancer studies are expected to drive transformative advancements in the field.This article is protected by copyright. All rights reserved

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Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications

et al. 2023

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Cancer kills millions of individuals every year all over the world (Global Cancer Observatory). The physiological and biomechanical processes underlying the tumor are still poorly understood, hindering researchers from creating new, effective therapies. Inconsistent results of preclinical research, in vivo testing, and clinical trials decrease drug approval rates. 3D tumor‐on‐a‐chip (ToC) models integrate biomaterials, tissue engineering, fabrication of microarchitectures, and sensory and actuation systems in a single device, enabling reliable studies in fundamental oncology and pharmacology. This review includes a critical discussion about their ability to reproduce the tumor microenvironment (TME), the advantages and drawbacks of existing tumor models and architectures, major components and fabrication techniques. The focus is on current materials and micro/nanofabrication techniques used to manufacture reliable and reproducible microfluidic ToC models for large‐scale trial applications.

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Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread

Cited by 39 publications

References 78 publications

Multiplexed imaging and effluent analysis to monitor cancer cell intravasation using a colorectal cancer-on-chip

Multiplexed imaging and effluent analysis to monitor cancer cell intravasation using a colorectal cancer-on-chip

Cancer Metastasis‐on‐a‐Chip for Modeling Metastatic Cascade and Drug Screening

Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications

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