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Oncogene. 2016 Dec 8;35(49):6309-6318. doi: 10.1038/onc.2016.161. Epub 2016 May 16.

A CCL8 gradient drives breast cancer cell dissemination.

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Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC, USA.
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
Department of Basic Sciences, Dental School, University of Athens, Athens, Greece.
Department of Biochemistry, University of Athens Medical School, Athens, Greece.


The migration of cancer cells towards gradients of chemoattractive factors represents a potential, yet elusive, mechanism that may contribute to cancer cell dissemination. Here we provide evidence for the maintenance of a gradient of increasing CCL8 concentration between the epithelium, the stroma and the periphery that is instrumental for breast cancer cells' dissemination. In response to signals elicited by the neoplastic epithelium, CCL8 production is enhanced in stromal fibroblasts at the tumor margins and in tissues at which breast cancer cells tend to metastasize such as the lungs and the brain. Manipulation of CCL8 activity influences the histology of the tumors and promotes major steps of the metastatic process such as invasion to adjacent stroma, intravasation and ultimately extravasation and seeding. These findings exemplify how gradients of chemoattractive factors such as CCL8, drive metastasis and suggest that interference with their operation may provide means for breast cancer management.

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