Blocking surgically induced lysyl oxidase activity reduces the risk of lung metastases
Rachman-Tzemah, Chen; Zaffryar-Eilot, Shelly; Grossman, Moran; Ribero, Dario; Timaner, Michael; Mäki, Joni M.; Myllyharju, Johanna; Bertolini, Francesco; Hershkovitz, Dov; Sagi, Irit; Hasson, Peleg; Shaked, Yuval (2017-04-25)
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M. Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked, Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases, Cell Reports, Volume 19, Issue 4, 2017, Pages 774-784, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2017.04.005. (http://www.sciencedirect.com/science/article/pii/S2211124717304783)
© 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distantmetastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.
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