Data from Lysyl Oxidase Is a Strong Determinant of Tumor Cell Colonization in Bone

• DOI: 10.1158/0008-5472.c.6508325.v1
• Publication Date: 2023-03-31T22:38:19Z
• Authors: Caroline Reynaud; Laura Ferreras; Paola Di Mauro; Casina Kan; Martine Croset; Edith Bonnelye; Floriane Pez; Clémence Thomas; Géraldine Aimond; Antoine E. Karnoub; Marie Brevet; Philippe Clézardin
• Keywords: Lysyl Oxidase

<div>Abstract<p>Lysyl oxidase (LOX) is a secreted copper-dependent amine whose primary function to drive collagen crosslinking and extracellular matrix stiffness. LOX in colorectal cancer synergizes with hypoxia-inducible factor-1 (HIF-1) promote tumor progression. Here we investigated whether LOX/HIF1 endows cells full competence for aggressive colonization bone. We show that high <i>LOX</i> expression tumors from patients was associated poor clinical outcome, irrespective of <i>HIF-1</i>. In addition, expressed by the bone marrow metastases. <i>In vivo</i> experimental studies overexpression or systemic delivery conditioned medium <i>LOX</i>-overexpressing promoted cell dissemination enhanced osteolytic lesion formation, Conversely, silencing pharmacologic inhibition activity blocked tumor-driven formation. vitro</i>, tumor-secreted supported attachment survival matrix, inhibited osteoblast differentiation. also induced robust production IL6. turn, both IL6 were acting concert RANKL-dependent osteoclast differentiation, thereby creating an imbalance between resorption Collectively, our findings supports they reveal novel mechanism through which LOX-driven impairs homeostasis. <i>Cancer Res; 77(2); 268–78. ©2016 AACR</i>.</p></div>