Role of macrophages in metastasis

One of the hallmarks of cancer is its ability to spread and invade distant organs and tissues causing metastases. Although metastasis is triggered by multiple factors and involves a plethora of molecules, accumulating evidence points towards a role for macrophages.

Scientists on the EU-funded CANCER-3DMATRIX-EGF (Interactions of breast cancer cells with macrophages in controlled 3D in vitro microenvironments) project set out to study the mechanism underlying the interaction between macrophages and breast cancer cells. Their work focused on the epidermal growth factors (EGF) produced by macrophages and the EGF receptor (EGFR) expressed by breast cancer cells.

Their working hypothesis was that breast cancer cells and macrophages must come into contact to support metastasis. This was deducted from observations that breast cancer cells do not invade the collagen matrix when macrophages are absent, and that soluble EGF cannot stimulate breast cancer cell invasion in vitro. Since many chemo-attractants function by binding to the extracellular matrix, scientists set out to study the mode of activity of EGF.

In this context, researchers employed UV lithography to prepare 3D microenvironments for cell culture rich in extracellular matrix and macrophages. If EGF stayed on the surface of macrophages, then breast cancer cells would be unable to invade the matrix without coming into contact with macrophages. However, if EGF was released by macrophages and could function as a soluble factor or bind to the extracellular matrix, then breast cancer cells would show increased motility even if macrophages were localised remotely.

Scientists used confocal fluorescence microscopy to assay the behaviour of breast cancer cells in the presence of macrophages. Experimental observations suggested that EGF stimulated breast cancer cells through direct contact with macrophages.

Apart from fundamental knowledge into the role of EGF and macrophages in cancer metastasis, the CANCER-3DMATRIX-EGF findings have therapeutic implications. They indicate that blocking the interaction between cancer cells and macrophages could serve as a potential strategy for preventing metastasis.