How the matrix metalloproteinase MMP14 contributes to the progression of colorectal cancer
Lena Claesson-Welsh
Uppsala University, Beijer and Science for Life Laboratories, Department of Immunology, Genetics and Pathology, Uppsala, Sweden.
Address correspondence to: Lena Claesson-Welsh, Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Dag Hammarskjölds väg 20, 751 85 Uppsala, Sweden. Phone: 46.70.167.9260; Email: lena.welsh@igp.uu.se.
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First published February 4, 2020 - More info
© 2020 American Society for Clinical Investigation
Certain matrix metalloproteinase (MMP) family proteins have been associated with cell proliferation and invasion in aggressive cancers. However, attempts to target the MMPs with the hope of treating tumors have thus far failed. In this issue of the JCI, Ragusa and coworkers identified an intestinal cancer subgroup of slow-growing, chemotherapy-resistant, and very aggressive matrix-rich tumors that mimic a hard-to-treat colorectal cancer subtype in humans. These tumors showed downregulated levels of the transcription factor prospero homeobox protein 1 (PROX1), which relieved repression of the matrix metalloproteinase MMP14. Upregulated MMP14 levels correlated with blood vessel dysfunction and a lack of cytotoxic T cells. Notably, blockade of proangiogenic factors in combination with stimulation of the CD40 pathway in the mouse cancer model boosted cytotoxic T cell infiltration. The study illustrates how combinatorial treatments for aggressive, T cell–deficient cancers can launch an antitumor immune response.
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Copyright © 2020 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)