graphical abstract.16.01.19 copy

Cancer-associated macrophages have been studied for quite some time, but how they turned from good macrophages to bad macrophages was still unclear. The recent publication of Victoria Sanz-Moreno et al. from the Kings College of London on Cell has answer a lot of questions.

ROCK-Myosin II is well known to regulate amoeboid migration during invasion and metastasis. In an outstanding publication in Cell, Sanz-Moreno and colleagues have been able to identify how melanoma cells sitting at the leading edge of the tumor are able to control an immunomodulatory secretome mechanism that not only attracts monocyte to this site, but forces them to differentiate into cancer-associated macrophages promoting tumor growth. In fact, these amoeboid tumor cells present high levels of ROCK-Myosin activity, which is the master regulator of the immunomodulatory secretome.

Once the cancer-associated macrophages are in place next to the melanoma cancer cells, ROCK-myosin activity allows them to modulate the blood vessels around them enhancing tumor metastasis. And these behavior is continued due to the ROCK-myosin II-driven secretion of IL-1 alpha and NF-kB activation. Without any doubt,  this work will open novel therapeutic windows to inhibit the metastatic potential of melanoma cells.