page 977) find that the ability of tumor support cells to take in and degrade collagen helps tumor growth. Blocking the collagen uptake receptor, they show, keeps murine breast tumors in check.
Collagen, the major component of the extracellular matrix, can be degraded extracellularly by proteases or intracellularly in lysosomes. Mice lacking uPARAP, which mediates the uptake of collagen and thus the intracellular pathway, develop normally. The authors now show that these mice have an advantage over the wild type when it comes to controlling cancer progression.
Stromal cells surrounding breast tumors in the mutant mice did not take in and degrade collagen efficiently. Tumor growth was subsequently restricted in these mice. Proliferation and apoptosis rates of the tumor cells were unchanged, however, so the signals affected by collagen degradation that lead to tumor growth are still unclear.
Blocking the extracellular pathway is also known to limit tumor growth in mice, but this requires the inhibition of many proteases. The intracellular pathway, by contrast, can be blocked by disrupting only uPARAP. This strategy might be useful for the treatment of human cancers and other disorders involving the degradation of connective tissues, such as arthritis, which are all associated with strong intracellular collagen turnover.