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.
Cancer Sciences Unit, University of Southampton School of Medicine; University Surgical Unit, University of Southampton School of Medicine.
Marc D
MD
Bullock
Cancer Sciences Unit, University of Southampton School of Medicine.
Max
M
Mellone
Cancer Sciences Unit, University of Southampton School of Medicine.
Karen M
KM
Pickard
Cancer Sciences Unit, University of Southampton School of Medicine.
Abdulkadir Emre
AE
Sayan
Bioinformatics Unit, London Research Institute, Cancer Research UK.
Richard
R
Mitter
University Surgical Unit, University of Southampton School of Medicine.
John N
JN
Primrose
Cancer Sciences Unit, University of Southampton School of Medicine.
Graham K
GK
Packham
Cancer Sciences Unit, University of Southampton School of Medicine.
Gareth
G
Thomas
Cancer Sciences Unit, University of Southampton School of Medicine; University Surgical Unit, University of Southampton School of Medicine; a.h.mirnezami@soton.ac.uk.
Alexander H
AH
Mirnezami
D018920:Coculture Techniques / Q000379:methods*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D061346:Laser Capture Microdissection / Q000379:methods; D009361:Neoplasm Invasiveness; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment