Tumour growth and metastasis are dependent not only on the properties of the tumour itself, but also on the features of the surrounding normal tissue. Cells in the normal tissue environment, or stroma, are often altered to support the growth and eventual spreading of cancer cells to other organs. How the stroma interacts with the tumour is complex and all the signals between them are not fully known.
A new article by PM Cancer Centre Senior Scientist Dr. Rama Khokha identifies the TIMP family of proteins in the stroma as important for restricting tumour growth. Using experimental models and human tumour samples, Dr. Khokha found that loss of TIMPs changed normal cells in the stroma into cancer-associated fibroblast (CAF) cells. CAFs released "exosomes"—encapsulated cellular components—that interacted with tumour cells and helped them grow. Loss of TIMPs also enhanced the activity of enzymes within these exosomes to promote cancer growth and metastasis. Dr. Khokha explains, "We found that the Timp gene family governs the emergence of a CAF-like cell state, impacting tumour progression through a mode of stroma-tumour communication that activates key cancer-supporting pathways."
This study has revealed clues to the consequences of TIMP loss in cancer, and suggests that restoration of TIMP function in the tissue surrounding cancer may restrict tumour growth and metastasis.
This work was supported by the Canadian Institutes of Health Research, the Ontario Institute of Cancer Research and The Princess Margaret Cancer Foundation. T Kislinger is a Tier 2 Canada Research Chair in Proteomics in Cancer Research.
Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state. Shimoda M, Principe S, Jackson HW, Luga V, Fang H, Molyneux SD, Shao YW, Aiken A, Waterhouse PD, Karamboulas C, Hess FM, Ohtsuka T, Okada Y, Ailles L, Ludwig A, Wrana JL, Kislinger T, Khokha R . Nature Cell Biology. 2014 Sept. [Pubmed abstract]
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