Tumour-stroma interactions in cancer development

Lead Research Organisation: The Francis Crick Institute

Abstract

Cancer is not a self-sufficient entity: to grow it requires to co-opt the normal behaviour of many normal cells in order to receive essential support. This cancer-modified normal cells interaction drives all aspect of the tumour disease, from growth to metastatic spreading as well as resistance to anti-cancer therapy.
My laboratory aims to understand the strategy used by the cancer to perturb its surrounding tissue as well as the mechanism underlying the vital contribution of this corrupted normal tissue to the disease.
The aim of this research is to develop novel strategy to target the host tissue’s support to cancer cells. This will increase efficacy of cancer treatments.

Technical Summary

This work was supported by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001000), the Wellcome Trust (FC001000),and Cancer Research UK (FC001000)

Aim and importance of the research
The Tumour Host Interaction laboratory studies solid tumours (mainly breast, but also skin and lung cancer) in animal models focusing on the comprehensive analysis of cell–cell interactions within the entire tumour heterogeneity.
The lab focuses on the surrounding normal tissue cells that associate and functionally become part of the tumour mass. The host build the tumour microenvironment or niche which represents the cellular environment of cancer cells. The tumour niche contains a plethora of cell types that act in concert to support the tumour structure.
My lab studies the changes that cancer imposes on host tissue cells locally as well as the systemic changes that via the inflammatory cells extend to distant tissue. We study how those new environments support tumour growth and progression. Our aim is to identify and target these key tumour-host interactions to enhance anti-cancer therapies.
We investigate these questions using a combination of mouse genetic model and ex vivo co-culture systems.
Translational activities
My laboratory has identified a novel activity of systemically mobilized mature neutrophils within the pre-metastatic niche. We found that via the release of leukotrienes, pre-metastatic neutrophils selectively support the more metastatic subset of cancer cells infiltrating the distant tissue. Indeed, an inhibitor of leukotriene production reduces metastasis in vivo providing a strategy to block niche signal to reduce metastatic spreading (Wculek & Malanchi Nature 1–21 (2015)). The translational team of The Crick Institute in collaboration with prof Charles Coombes (Imperial College) is helping me to test a leukotrienes inhibitor drug on a sub-set of breast cancer patients at high risk for secondary relapses.

Publications

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