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Bone Abstracts (2016) 5 CABSOP3.2 | DOI: 10.1530/boneabs.5.CABS.OP3.2

ECTS2016 Cancer and Bone Oral Communications Oral Poster Talks (8 abstracts)

Lysyl oxidase promotes survival and outgrowth of colon cancer cells in the bone marrow, enabling bone metastasis formation

Caroline Reynaud 1, , Laura Ferreras 1, , Marie Brevet 1, & Philippe Clézardin 1,


1INSERM UMR1033, Lyon, France; 2University of Lyon, Vileurbanne, France; 3Hospices Civils de Lyon, Lyon; France.

Lysyl oxidase (LOX) catalyzes the cross-linking of collagens and elastin in the extracellular matrix, thereby regulating the tensile strength of many tissues, such as in bone. In cancer, LOX plays a critical role in facilitating tumor growth and metastasis formation in soft tissues. In this study, we first showed by immunohistochemistry using patients’ tumor specimens, that LOX was expressed in the desmoplastic tumor stroma of pairs of colorectal carcinomas and their matching bone metastases. Preclinical experiments showed that LOX overexpression in different colon carcinoma cells enhanced the formation of osteolytic lesions in animals by promoting both skeletal tumor burden and osteoclast-mediated bone resorption. Conversely, the pretreatment of animals with the LOX inhibitor β-aminopropionitrile or the silencing of LOX in colorectal carcinoma cells drastically reduced the formation of osteolytic lesions. Furthermore, we demonstrated that LOX was involved in the early nidation of tumor cells into the bone marrow. In vitro, LOX directly enhanced the attachment of colon cancer cells to type-I collagen, but not to fibronectin. LOX-overexpressing colorectal carcinoma cells were more prone to adhere to components of the osteoblastic niche, such as osteoblasts. Thus, LOX may promote engraftment of colon cancer cells in the osteoblastic niche. Tumor-derived LOX also promoted osteoclast differentiation by enhancing the secretion of osteolytic factors such as IL6. The activation of an IL6 autocrine loop led to cancer cell survival. In conclusion, our findings provide novel evidence that LOX endows colon cancer cells with the ability to thrive in the bone marrow microenvironment and stimulate osteoclast-mediated bone destruction.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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