Defining the pro-tumour impact of the evolving stromal microenvironment
type: CreativeWork
description: Much like normal tissues, tumours require a supporting microenvironment for growth and survival, known as the tumour stroma. However, tumours represent a dynamic and turbulent environment, in which factors such as hypoxia, fibrosis, nutrient deprivation and the local cytokine milieu continually fluctuate as the tumour grows and develops. These factors influence stromal phenotypes and create heterogeneity, which can confound our understanding of their role within the microenvironment. In particular, cancer associated fibroblasts (CAFs) represent a diverse population of cells, which cannot be identified by one universal marker. CAFs promote tumour growth and dissemination by secreting growth factors, stimulating angiogenesis, aiding the development of tumour-promoting inflammation and remodelling the extra-cellular matrix (ECM). However, recent investigations have shown these functions belong to defined populations that differ between tumour types. This project aimed to investigate stromal heterogeneity across melanoma development, with a specific focus on the CAF compartment. Whilst conventional techniques such as IF and flow cytometry showed varied expression of fibroblast markers, they lacked the resolution to discern functional subsets. Thus, we employed single cell RNA sequencing (scRNAseq) to profile CAF populations at different stages of tumour development. To avoid bias, CAFs were isolated from the B16-F10 melanoma model using a ‘negative selection’ approach. Our data revealed the presence of 3 functionally distinct fibroblast populations, termed ‘immune’, ‘desmoplastic’ and ‘contractile’, which expressed genes involved in immune cross talk, matrix remodelling and stress fibre contraction respectively. Furthermore, these populations are dynamic, changing in prevalence as the tumour grows. While ‘immune’ and ‘desmoplastic’ populations were present from early stages, ‘contractile’ CAFs were more abundant at later time points. Owing to their unique marker profile…
abstract: Much like normal tissues, tumours require a supporting microenvironment for growth and survival, known as the tumour stroma. However, tumours represent a dynamic and turbulent environment, in which factors such as hypoxia, fibrosis, nutrient deprivation and the local cytokine milieu continually fluctuate as the tumour grows and develops. These factors influence stromal phenotypes and create heterogeneity, which can confound our understanding of their role within the microenvironment. In particular, cancer associated fibroblasts (CAFs) represent a diverse population of cells, which cannot be identified by one universal marker. CAFs promote tumour growth and dissemination by secreting growth factors, stimulating angiogenesis, aiding the development of tumour-promoting inflammation and remodelling the extra-cellular matrix (ECM). However, recent investigations have shown these functions belong to defined populations that differ between tumour types. This project aimed to investigate stromal heterogeneity across melanoma development, with a specific focus on the CAF compartment. Whilst conventional techniques such as IF and flow cytometry showed varied expression of fibroblast markers, they lacked the resolution to discern functional subsets. Thus, we employed single cell RNA sequencing (scRNAseq) to profile CAF populations at different stages of tumour development. To avoid bias, CAFs were isolated from the B16-F10 melanoma model using a ‘negative selection’ approach. Our data revealed the presence of 3 functionally distinct fibroblast populations, termed ‘immune’, ‘desmoplastic’ and ‘contractile’, which expressed genes involved in immune cross talk, matrix remodelling and stress fibre contraction respectively. Furthermore, these populations are dynamic, changing in prevalence as the tumour grows. While ‘immune’ and ‘desmoplastic’ populations were present from early stages, ‘contractile’ CAFs were more abundant at later time points. Owing to their unique marker profile…
author: Davidson, Sarah
language: eng
keywords: Cancer, CAFs, Single Cell Sequencing
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/09954f7e-c227-4821-a8c1-5197bff81dae/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020-10-26
date modified: 2026-07-22T22:24:30Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.55840