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

Autor: Jasmer KJ; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA. Jasmerk@missouri.edu.; Department of Biochemistry, University of Missouri, Columbia, MO, USA. Jasmerk@missouri.edu., Shanbhag VC; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Forti KM; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Woods LT; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Gudekar NS; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA., Weisman GA; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA., Petris MJ; Christopher S. Bond Life Sciences Center 540F, University of Missouri, 1201 E Rollins, Columbia, MO, 65211, USA.; Department of Biochemistry, University of Missouri, Columbia, MO, USA.; Department of Ophthalmology, University of Missouri, Columbia, MO, USA.
Jazyk: angličtina
Zdroj: Clinical & experimental metastasis [Clin Exp Metastasis] 2024 Dec 23; Vol. 42 (1), pp. 7. Date of Electronic Publication: 2024 Dec 23.
DOI: 10.1007/s10585-024-10325-y
Abstrakt: Copper promotes tumor growth and metastasis through a variety of mechanisms, most notably as a cofactor within the lysyl oxidase (LOX) family of secreted cuproenzymes. Members of this family, which include LOX and LOX-like enzymes LOXL1-4, catalyze the copper-dependent crosslinking of collagens and elastin within the extracellular matrix (ECM). Elevated LOX expression is associated with higher incidence and worse prognosis in multiple cancers, including colorectal, breast, pancreatic, and head and neck. In this study, we demonstrated that elevated LOX expression correlates with decreased overall survival and shorter median time to first progression in patients with lung cancer. Previous studies have demonstrated that LOX secreted from tumors is critical for pre-metastatic niche formation by promoting ECM remodeling and the recruitment of immune cells and endothelial precursors. Here, we demonstrated that ablation of the LOX gene in Lewis lung carcinoma (LLC) cells diminishes tumor growth and metastasis compared to wild-type LLC cells in a syngeneic mouse model. Although the role of tumor-derived LOX in tumor formation and metastasis is well established, little is known regarding the possible contribution of LOX produced by the parenchymal tissue of metastatic organs. Thus, this report describes our findings that host-derived LOX produced by the lung contributes to the pulmonary metastasis of LLC cells in mice. The suppression of pulmonary lysyl oxidase expression reduces the metastatic potential of Lewis Lung Carcinoma cells in mice, revealing a previously unknown influence of LOX expression in the parenchymal tissue of metastatic target organs on the seeding of tumor cells.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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