The role of cancer-associated fibroblasts (CAFs) as regulators of tumor progression, specifically vascular growth, has only recently been described. CAFs are thought to be more mechanically active but how this trait may alter the tumor microenvironment is poorly understood. We hypothesized that enhanced mechanical activity of CAFs, as regulated by the Rho/ROCK pathway, contributes to increased blood vessel growth. Using a 3D in vitro tissue model of vasculogenesis, we observed increased vascularization in the presence of breast cancer CAFs compared to normal breast fibroblasts. Further studies indicated this phenomenon was not simply a result of enhanced soluble signaling factors, including vascular endothelial growth factor (VEGF), and that CAFs generated significantly larger deformations in 3D gels compared to normal fibroblasts. Inhibition of the mechanotransductive pathways abrogated the ability of CAFs to deform the matrix and suppressed vascularization. Finally, utilizing magnetic microbeads to mechanically stimulate mechanically-inhibited CAFs showed partial rescue of vascularization. Our studies demonstrate enhanced mechanical activity of CAFs may play a crucial and previously unappreciated role in the formation of tumor-associated vasculature which could possibly offer potential novel targets in future anti-cancer therapies.

In the early 1930s Aaron Copland began to compose in an accessible idiom he described as “imposed simplicity.” Many works written within this style, including El Salón México, the Fanfare for the Common Man, and the Third Symphony, have come to epitomize a nostalgic Americanism and sentimental populism. Yet the relatively simple surface of Copland's music belies a complex aesthetic ideology that owes to a tradition of progressive politics in the context of the Popular Front. Recent revisionist historiography understands the Front as a cultural force extending from the late 1920s through the war years and advocating a social-democratic politics, reform of corporate capitalism, and multiethnic solidarity. These ideals can be read in the aesthetic ideology of Copland's music of the same era. El Salón México (1932), for example, draws upon working-class ethnic culture to mount a critique of industrial modernism, while the Third Symphony (1946) and its hommage to the “common man” evoke a radical populism to project a progressive vision of social justice. In contrast to portrayals of the composer as merely sympathetic to the cultural forces of depression and war, Copland was a politically engaged and ideologically aligned artist working within what historian Michael Denning has called “the cultural front.”

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