Interactions between tumor cells and other cell types in the surrounding microenvironment (stroma) are crucial for tumor cell growth, survival and metastatic spread. Although tumor cells are known to induce mechanical changes in their microenvironment, few studies have examined the effect of mechanical stimuli on stromal cells such as fibroblasts.
Donna Webb, Ph.D., Deyu Li, Ph.D., and colleagues used a microfluidic platform to study the effects of “stretching” human prostatic fibroblasts. They report Feb. 9 in Scientific Reports that mechanical stretching of normal tissue-associated fibroblasts (NAFs) alters the structure of the extracellular matrix protein fibronectin. While unstretched NAFs deposit and assemble fibronectin in a random, mesh-like arrangement, stretched NAFs produce matrix with a more organized, linearly aligned structure. Stretched NAFs also directed co-cultured cancer cell migration and had biochemical changes consistent with those observed in cancer-associated fibroblasts.
The findings suggest that mechanical stress is a critical factor in activating NAFs to generate cancer-associated fibroblasts.
This work was supported by grants from the National Institutes of Health (CA155572, GM092914, RR025524).
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