Fig. 5.

Strategies to alleviate growth-induced solid stress in tumors. (Middle) In an untreated tumor, proliferating cancer cells and activated fibroblasts deform the ECM, resulting in stretched collagen fibers, compressed hyaluronan, and deformed cells—all storing solid stress. This stress compresses intratumor blood and lymphatic vessels. Potential strategies to alleviate solid stress and decompress vessels involve depleting these components. Depleting cancer cells (Top Left) or fibroblasts (Top Right) relaxes collagen fibers, hyaluronan, and the remaining cells, alleviating solid stress. Depleting collagen (Bottom Left) alleviates the stress that was held within these fibers as well as relaxes stretched/activated fibroblasts and compressed cancer cells within nodules. Finally, depleting hyaluronan (Bottom Right) alleviates the stored compressive stress, allowing nearby components to decompress. (Note that other stromal cells, such as pericytes, macrophages, and various immune cells that might also control production of collagen or hyaluronan, are not shown to simplify the schematic. Lymphatic vessels are also not shown for the same reason.)