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Lysyl oxidase plays a pivotal role in promoting metastasis of breast cancer cells
El-Haibi et al. demonstrate that human breast cancer cells cocultured with human bone marrow-derived mesenchymal stem cells (MSCs) show enhanced expression of many genes, including those involved with extracellular matrix (ECM) maturation. One of the most highly induced genes was shown to code for lysyl oxidase (LOX), an amine oxidase enzyme that catalyzes cross-linking between collagens and elastins in the ECM.
MSCs appear to enhance de novo production of LOX in breast cancer cells. LOX overexpression completely changes the characteristics and behaviour of the previously non-invasive cancer cells, causing them to lose their epithelial phenotype and to acquire mesenchymal traits. Further analysis revealed that Twist, one of the EMT-linked transcription factors, was expressed at 25–50 times baseline levels in breast cancer cells showing significant LOX overexpression. Within the ECM, the study identified hyaluronan as the likely regulator of LOX induction. This glycosaminoglycan acts through the CD44 receptor, inducing Twist expression in the breast cells and pushing them towards epithelial-to-mesenchymal transition.
Although MSCs promote LOX overexpression in breast cancer cells and enable them to metastasize to sites such as lung and bone, this interaction is not involved in the expansion of cancer stem cells.
Editor’s comment: These findings uncover a previously unknown role for lysyl oxidase in mediating epithelial-to-mesenchymal transition of breast cancer cells.
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