Nature Cancer: Reprogrammed macrophages stimulate vascular cells to secrete proteins and promote cancer metastasis

Research by scientists at the German Cancer Research Center (DKFZ) and HI-STEM has found that metastatic breast cancer cells use macrophages, a type of immune cell, to promote the resolution of lung cancer metastasis

Research team leader Dr Thordur Oskarsson from DKFZ and HI-STEM said: "The complexity of the interactions between cancer cells, macrophages and endothelial cells is striking

Oskarsson and colleagues published the paper in the journal Nature Cancer

Cancer cells spread throughout the body, with individual cells detached from the primary tumor and metastasized to distant areas of the body through the blood or lymphatic system

Blood vessels play a very specific role in metastasis

Oskarsson and colleagues investigated the interaction between cancer cells and ECs during the metastatic colonization of breast cancer cells in the lungs of experimental mice

Importantly, high expression of these four newly discovered niche factors was also found to be associated with shorter recurrence-free survival and overall survival in breast cancer patients

But how do cancer cells acquire the lung endothelium to produce a cocktail of proteins that promote metastasis? To the scientists' surprise, the cancer cells themselves did not do the job directly, but instead used macrophages, a type of cells of the innate immune system type

"These macrophages normally reside near pulmonary blood vessels and are activated by tenascin, an extracellular matrix protein produced by breast cancer cells," explained Tsunaki Hongu, PhD, a HI-STEM postdoc and first author of the study

The researchers eliminated macrophages or their activity using specific molecular preparations to demonstrate that these cells are critical for producing a protein cocktail that promotes metastasis

The team concludes that their results provide new insights into the role of the extracellular matrix in cancer metastasis and point to potential therapeutic avenues