Molecular profiling of the invasive tumor microenvironment in a 3-dimensional model of colorectal cancer cells and ex vivo fibroblasts
Molecular profiling of the invasive tumor microenvironment in a 3-dimensional model of colorectal cancer cells and ex vivo fibroblasts
Invading colorectal cancer (CRC) cells have acquired the capacity to break free from their sister cells, infiltrate the stroma, and remodel the extracellular matrix (ECM). Characterizing the biology of this phenotypically distinct group of cells could substantially improve our understanding of early events during the metastatic cascade.
Tumor invasion is a dynamic process facilitated by bidirectional interactions between malignant epithelium and the cancer associated stroma. In order to examine cell-specific responses at the tumor stroma-interface we have combined organotypic co-culture and laser micro-dissection techniques.
Organotypic models, in which key stromal constituents such as fibroblasts are 3-dimensionally co-cultured with cancer epithelial cells, are highly manipulatable experimental tools which enable invasion and cancer-stroma interactions to be studied in near-physiological conditions.
Laser microdissection (LMD) is a technique which entails the surgical dissection and extraction of the various strata within tumor tissue, with micron level precision.
By combining these techniques with genomic, transcriptomic and epigenetic profiling we aim to develop a deeper understanding of the molecular characteristics of invading tumor cells and surrounding stromal tissue, and in doing so potentially reveal novel biomarkers and opportunities for drug development in CRC.
colorectal cancer, cancer metastasis, organotypic culture, laser microdissection, molecular profiling, invasion, tumor microenvironment, stromal tissue, epithelium, fibroblasts
Bullock, Marc D.
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Mellone, Max
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Pickard, Karen M.
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Sayan, Abdulkadir Emre
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Mitter, Richard
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Primrose, John N.
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Packham, Graham K.
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Thomas, Gareth
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Mirnezami, Alexander H.
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29 April 2014
Bullock, Marc D.
e060d2b2-5e6f-449b-b8ae-f411b5a396c2
Mellone, Max
b0301b32-14f8-4203-9026-b7f90885cab9
Pickard, Karen M.
e5188669-dff1-49c7-9c6f-8122b0c74bd9
Sayan, Abdulkadir Emre
d1dbbcad-9c53-47c1-8b7e-1b45cc56e077
Mitter, Richard
5d4318fc-b6da-4a5b-8a88-5815e9e51b9a
Primrose, John N.
d85f3b28-24c6-475f-955b-ec457a3f9185
Packham, Graham K.
fdabe56f-2c58-469c-aadf-38878f233394
Thomas, Gareth
2ff54aa9-a766-416b-91ee-cf1c5be74106
Mirnezami, Alexander H.
b3c7aee7-46a4-404c-bfe3-f72388e0bc94
Bullock, Marc D., Mellone, Max, Pickard, Karen M., Sayan, Abdulkadir Emre, Mitter, Richard, Primrose, John N., Packham, Graham K., Thomas, Gareth and Mirnezami, Alexander H.
(2014)
Molecular profiling of the invasive tumor microenvironment in a 3-dimensional model of colorectal cancer cells and ex vivo fibroblasts.
Journal of Visualized Experiments, 86.
(doi:10.3791/51475).
(PMID:24836208)
Abstract
Invading colorectal cancer (CRC) cells have acquired the capacity to break free from their sister cells, infiltrate the stroma, and remodel the extracellular matrix (ECM). Characterizing the biology of this phenotypically distinct group of cells could substantially improve our understanding of early events during the metastatic cascade.
Tumor invasion is a dynamic process facilitated by bidirectional interactions between malignant epithelium and the cancer associated stroma. In order to examine cell-specific responses at the tumor stroma-interface we have combined organotypic co-culture and laser micro-dissection techniques.
Organotypic models, in which key stromal constituents such as fibroblasts are 3-dimensionally co-cultured with cancer epithelial cells, are highly manipulatable experimental tools which enable invasion and cancer-stroma interactions to be studied in near-physiological conditions.
Laser microdissection (LMD) is a technique which entails the surgical dissection and extraction of the various strata within tumor tissue, with micron level precision.
By combining these techniques with genomic, transcriptomic and epigenetic profiling we aim to develop a deeper understanding of the molecular characteristics of invading tumor cells and surrounding stromal tissue, and in doing so potentially reveal novel biomarkers and opportunities for drug development in CRC.
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Published date: 29 April 2014
Keywords:
colorectal cancer, cancer metastasis, organotypic culture, laser microdissection, molecular profiling, invasion, tumor microenvironment, stromal tissue, epithelium, fibroblasts
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 373975
URI: http://eprints.soton.ac.uk/id/eprint/373975
ISSN: 1940-087X
PURE UUID: a46c402c-6083-4771-9218-4883ddc9fc59
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Date deposited: 04 Feb 2015 14:26
Last modified: 15 Mar 2024 03:37
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Contributors
Author:
Marc D. Bullock
Author:
Max Mellone
Author:
Karen M. Pickard
Author:
Richard Mitter
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