Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Apr 27

PMID 28445728

Citations 61

Authors

Chen Rachman-Tzemah

Shelly Zaffryar-Eilot

Moran Grossman

Dario Ribero

Michael Timaner

Joni M Maki

Johanna Myllyharju

Francesco Bertolini

Dov Hershkovitz

Irit Sagi

Peleg Hasson

Yuval Shaked

Affiliations

Soon will be listed here.

Abstract

Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. 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.

Citing Articles

Pulmonary lysyl oxidase expression and its role in seeding Lewis lung carcinoma cells.

Jasmer K, Shanbhag V, Munoz Forti K, Woods L, Gudekar N, Weisman G Clin Exp Metastasis. 2024; 42(1):7.

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The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics.

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LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.

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Cancer treatments as paradoxical catalysts of tumor awakening in the lung.

Nicolas E, Kosmider B, Cukierman E, Borghaei H, Golemis E, Borriello L Cancer Metastasis Rev. 2024; 43(4):1165-1183.

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