Tumor model for breast cancer cell migration studies and related methods
Patent Number: US20170067025
Executive Summary:
This invention is a method for creating a tumor model includes encapsulating cancer cells in a first solution, disposing the first solution on a spacer, cross-linking the first solution and creating one or more high stiffness constructs, disposing a second solution around the one or more high stiffness constructs, and cross-linking the second solution and creating a low stiffness matrix surrounding the one or more low stiffness constructs.
General Description:
Metastatic dissemination of cancer cells is a highly complex and multi-step biological process starting with tumor angiogenesis and the invasion of cancer cells through the extracellular (ECM) matrix toward the blood vessels. Cancer cell invasion through the tumor stroma is governed by diverse factors including biochemical signals and biophysical cues. Despite their significance, most in vivo animal models present an abundance of confounding variables making it challenging to attribute specific microenvironmental cues to cellular invasion. In this regard, physiologically relevant in vitro tumor models are crucial to understand cancer cell invasion within a native-like breast tumor microenvironment.
In the past few years, there has been a tremendous initiative to develop in vitro models to study cancer cell behavior in 3D microenvironments. For instance, three-dimensional (3D) surface topographies have been widely used to study cancer cell behavior in response to various geometrical features. Despite their significance, these platforms lacked the capacity for varying parameters including stiffness and matrix architecture. Alternatively, a wide variety of 3D hydrogel-based matrices such as Matrigel, fibrin, collagen, and polyethylene glycol (PEG) have shown great promise to recapitulate cancer cell invasion in a 3D matrix and assess cellular behavior in response to various biophysical and biochemical cues. Such 3D hydrogel-based matrices enable cells to retain accurate phenotype and, consequently, exhibit precise responses to microenvironmental stimuli along with cell-cell and cell-matrix interactions. These models, however, lack specific patterned features that would enable precise control over cellular distribution and matrix stiffness to conduct studies within biomimetic tumor architecture.
This invention describes a method for creating a tumor model includes encapsulating cancer cells in a first solution, disposing the first solution on a spacer, cross-linking the first solution and creating one or more high stiffness constructs, disposing a second solution around the one or more high stiffness constructs, and cross-linking the second solution and creating a low stiffness matrix surrounding the one or more low stiffness constructs. This method will be able to re-capitulate the behaviors of cancer cells in vivo to provide a more accurate model for testing cancer therapeutics especially for metastatic cancers.
Strengths:
Patent Status:
Priority date 2015-09-02
Filing date 2016-08-31
Publication date 2017-03-09
Publications:
1. N. Peela#, F. S. Sam#, W. Christenson, D. Truong, A. W. Watson, G. Mouneimne, R. Ros, M. Nikkhah*, “A Three Dimensional Micropatterned Tumor Model for Breast Cancer Cell Migration Studies”, Biomaterials, 81: 72-83, 2016. [#Equal Contribution].
2. D. Truong, J. Puleo, A. Llave, G. Mouneimne, R. D. Kamm, and M. Nikkhah*, “Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment,”Scientific Reports, 6: 34094, 2016.
3. N. Peela#, D. Truong#, H. Saini#, H. Chu, S. Mashaghi, S. L. Ham, S. Singth, H. Tavana, B. Mossadegh, M. Nikkhah*, “Advanced Biomaterials and Microengineering Technologies to Recapitulate the Stepwise Process of Cancer Metastasis”, Biomaterials, Accepted, (In Press), 2017.
Inventor Bio: Mehdi Nikkhah
https://sbhse.engineering.asu.edu/faculty-and-staff/faculty/mehdi-nikkhah/
Executive Summary:
This invention is a method for creating a tumor model includes encapsulating cancer cells in a first solution, disposing the first solution on a spacer, cross-linking the first solution and creating one or more high stiffness constructs, disposing a second solution around the one or more high stiffness constructs, and cross-linking the second solution and creating a low stiffness matrix surrounding the one or more low stiffness constructs.
- Invention Type: Device
- Patent Status: Patent pending
- Patent Link: https://patents.google.com/patent/US20170067025/
- Research Institute: Arizona State University
- Disease Focus: Cancer and related diseases
- Basis of Invention: This invention describes a tumor model that recapitulates the tumor micro-environment to study the behavior of cancer cells
- How it works: This invention describes a method for creating a tumor model, includes encapsulating cancer cells in a first solution, disposing the first solution on a spacer, cross-linking the first solution and creating one or more high stiffness constructs, disposing a second solution around the one or more high stiffness constructs, and cross-linking the second solution and creating a low stiffness matrix surrounding the one or more low stiffness constructs.
- Lead Challenge Inventor: Mehdi Nikkhah
- Inventors: Mehdi Nikkhah, Feba Sam, Nitish Peela
- Development Stage: Pre-clinical, in vitro assays data available
- Novelty:
- Besides 3D cancer cell culture, also added stiffness of the matrix in 3D to simulate the micro-environment of cancer cells
- Clinical Applications:
- In vitro drug testing for metastatic cancers
General Description:
Metastatic dissemination of cancer cells is a highly complex and multi-step biological process starting with tumor angiogenesis and the invasion of cancer cells through the extracellular (ECM) matrix toward the blood vessels. Cancer cell invasion through the tumor stroma is governed by diverse factors including biochemical signals and biophysical cues. Despite their significance, most in vivo animal models present an abundance of confounding variables making it challenging to attribute specific microenvironmental cues to cellular invasion. In this regard, physiologically relevant in vitro tumor models are crucial to understand cancer cell invasion within a native-like breast tumor microenvironment.
In the past few years, there has been a tremendous initiative to develop in vitro models to study cancer cell behavior in 3D microenvironments. For instance, three-dimensional (3D) surface topographies have been widely used to study cancer cell behavior in response to various geometrical features. Despite their significance, these platforms lacked the capacity for varying parameters including stiffness and matrix architecture. Alternatively, a wide variety of 3D hydrogel-based matrices such as Matrigel, fibrin, collagen, and polyethylene glycol (PEG) have shown great promise to recapitulate cancer cell invasion in a 3D matrix and assess cellular behavior in response to various biophysical and biochemical cues. Such 3D hydrogel-based matrices enable cells to retain accurate phenotype and, consequently, exhibit precise responses to microenvironmental stimuli along with cell-cell and cell-matrix interactions. These models, however, lack specific patterned features that would enable precise control over cellular distribution and matrix stiffness to conduct studies within biomimetic tumor architecture.
This invention describes a method for creating a tumor model includes encapsulating cancer cells in a first solution, disposing the first solution on a spacer, cross-linking the first solution and creating one or more high stiffness constructs, disposing a second solution around the one or more high stiffness constructs, and cross-linking the second solution and creating a low stiffness matrix surrounding the one or more low stiffness constructs. This method will be able to re-capitulate the behaviors of cancer cells in vivo to provide a more accurate model for testing cancer therapeutics especially for metastatic cancers.
Strengths:
- Add the matrix stiffness in 3D culture for cancer cells
Patent Status:
Priority date 2015-09-02
Filing date 2016-08-31
Publication date 2017-03-09
Publications:
1. N. Peela#, F. S. Sam#, W. Christenson, D. Truong, A. W. Watson, G. Mouneimne, R. Ros, M. Nikkhah*, “A Three Dimensional Micropatterned Tumor Model for Breast Cancer Cell Migration Studies”, Biomaterials, 81: 72-83, 2016. [#Equal Contribution].
2. D. Truong, J. Puleo, A. Llave, G. Mouneimne, R. D. Kamm, and M. Nikkhah*, “Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment,”Scientific Reports, 6: 34094, 2016.
3. N. Peela#, D. Truong#, H. Saini#, H. Chu, S. Mashaghi, S. L. Ham, S. Singth, H. Tavana, B. Mossadegh, M. Nikkhah*, “Advanced Biomaterials and Microengineering Technologies to Recapitulate the Stepwise Process of Cancer Metastasis”, Biomaterials, Accepted, (In Press), 2017.
Inventor Bio: Mehdi Nikkhah
https://sbhse.engineering.asu.edu/faculty-and-staff/faculty/mehdi-nikkhah/