Immune Cells Play Key Role in Early Breast Cancer Metastasis Even Before a Tumor Develops

Source: The Mount Sinai Hospital

Summary: Researchers have discovered that normal immune cells play a major role in helping early breast cancer cells leave the breast for other parts of the body, potentially creating metastasis before a tumor has even developed.

Cancer cell dissemination during early stages of breast cancer proceeds through poorly understood mechanisms. The important cells of the innate immune system, macrophages, play a role in mammary gland development by regulating how milk ducts branch out through breast tissue. Also, previous studies have proven the importance of macrophages in metastasis, but until now, only in models of advanced large tumors.

Researchers from the Mount Sinai Hospital have discovered that macrophages, which reside in healthy breast tissue surrounding milk ducts play a major role in helping early breast cancer cells leave the breast for other parts of the body, potentially creating metastasis before a tumor has even developed. By studying human samples, mouse tissues, and breast organoids, the new research found that in very early cancer lesions, macrophages are attracted to enter the breast ducts where they trigger a chain reaction that brings early cancer cells out of the breast. The research findings were published in the journal Nature Communications.

Macrophages play a role early metastasis

Macrophages orchestrate breast cancer early dissemination and metastasis. Credit: Nina Linde et al/The Mount Sinai Hospital/Nature Communications

This research shows that macrophages’ relationship with normal breast cells is co-opted by early cancer cells that activate the cancercausing HER2 gene, helping in this newly-discovered role of these immune cells. Early treatment of high-risk patients may prevent the formation of deadly metastasis better than the current standard of treating metastatic disease only once it has occurred. The findings from this study could eventually help pinpoint biomarkers to identify cancer patients who may be at risk of carrying potential metastatic cells due to these macrophages and potentially lead to the development of novel therapies that prevent early cancer metastasis.

Researcher Miriam Merad, MD, PhD said, “Here, we have identified how macrophages and early cancer cells form a ‘microenvironment of early dissemination’ and show that by disrupting this interaction we can prevent early dissemination and ultimately deadly metastasis”, “This sheds light onto the mysterious process of early dissemination and for patients who have metastasis cancer that came from an unknown source.”

More Information: Nina Linde et al, “Macrophages orchestrate breast cancer early dissemination and metastasis”, Nature Communications (2017).DOI:10.1038/s41467-017-02481-5

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