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) Keywords: surgery; pre-metastatic niche; metastasis; breast cancer; lysyl oxidase; hypoxia; host response
Blocking surgically induced lysyl oxidase activity reduces the risk of lung metastases
|Author:||Rachman-Tzemah, Chen1; Zaffryar-Eilot, Shelly2; Grossman, Moran3;|
1Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
2Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
3Biological Regulation, Weizmann institute of Science, Rehovot 7610001, Israel
4Department of Hepatobiliary and Pancreatic Surgery, European Institute of Oncology, Milan 20141, Italy
5Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90220, Finland
6Laboratory of Hematology-Oncology, European Institute of Oncology, Milan 20141, Italy
7Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel
|Online Access:||PDF Full Text (PDF, 2.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201802153438
|Publish Date:|| 2018-02-15
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.
|Pages:||774 - 784|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work is primarily supported by the European Research Council (grant 260633, Y.S.) and Rappaport Institute (Y.S. and P.H.) J.M. was supported by the Academy of Finland Center of Excellence (grant 251314), the S. Juselius Foundation, and the Jane and Aatos Erkko Foundation. F.B. is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC).
|Academy of Finland Grant Number:||
251314 (Academy of Finland Funding decision)
© 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/).