Writing in the journal Genes & Development, Dr. Johanna Joyce and colleagues at Memorial Sloan Kettering Cancer Center lend new insight into the mechanism by which tumor-associated macrophages promote malignant progression.

Innate immune cells, including macrophages, comprise a large fraction of the cellular environment that infiltrates tumors – the so-called "tumor microenvironment." Tumors have a dynamic relationship with their microenvironment, communicating via secreted factors to modulate cellular growth and cancer progression.

In their paper, Joyce and colleagues delineate how tumor-associated macrophages (TAMs) promote tumor growth and invasion. The researchers found that macrophage cells infiltrating pancreatic, mammary and lung tumors produce high levels of the proteases cathepsin B and S (Cts B and S), which enhances tumor growth and invasion. Interestingly, the researchers discovered that increased Cts B and S activity is stimulated by the tumors, themselves – through the release of interleukin (IL)-4.

The study is highly anticipated because it provides novel and compelling evidence for the therapeutic targeting of the tumor microenvironment – specifically TAMs – to disrupt communication and ultimately impede cancer progression.

Joyce is optimistic that "the identification of factors that are differentially produced by conscripted cells in the tumor microenvironment provides a strategy to selectively target these cells in combination with targeting the cancer cells, an approach that could have significant therapeutic potential."

SOURCES:
Genes & Development, February 1, 2010
Cold Spring Harbor Laboratory (http://www.cshl.edu)