Abstract
Breast cancer preferentially metastasizes to lung, lymph node, liver, bone, and brain. However, it is unclear whether properties of cancer cells, properties of organ microenvironments, or a combination of both is responsible for this observed organ tropism.
We hypothesized that breast cancer cells exhibit distinctive migration/growth patterns in organ microenvironments that mirror common clinical sites of breast cancer metastasis and that receptor-ligand interactions between breast cancer cells and soluble organ-derived factors mediate this behavior. Using an ex vivo model system composed of organ-conditioned media (CM), human breast cancer cells (MDA-MB-231, MDA-MB-468, SUM149, and SUM159) displayed cell line–specific and organ-specific patterns of migration/proliferation that corresponded to their in vivo metastatic behavior. Notably, exposure to lung-CM increased migra- tion of all cell lines and increased proliferation in two of four lines (P < .05).
Several cluster of differentiation (CD) 44 ligands including osteopontin (OPN) and L-selectin (SELL) were identified in lung-CM by protein arrays. Immunodepletion of SELL decreased migration of MDA-MB-231 cells, whereas depletion of OPN decreased both migration and proliferation. Pretreatment of cells with a CD44-blocking antibody abrogated migration effects (P < .05). “Stemlike” breast cancer cells with high aldehyde dehydrogenase and CD44 (ALDHhiCD44+) responded in a distinct chemotactic manner toward organ-CM, preferentially migrating toward lung-CM through CD44 receptor-ligand interactions (P < .05).
In contrast, organ-specific changes in migration were not observed for ALDHlowCD44− cells. Our data suggest that interactions between CD44+ breast cancer cells and soluble factors present in the lung microenvironment may play an important role in determining organotropic metastatic behavior.
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Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.
Available online 4 April 2014
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Citation: [Chu JE, Xia Y, Chin-Yee B, Goodale D, Croker AK, Allan AL. Lung-Derived Factors Mediate Breast Cancer Cell Migration through CD44 Receptor-Ligand Interactions in a Novel Ex Vivo System for Analysis of Organ-Specific Soluble Proteins. Neoplasia [Internet]. 2014 Feb [cited 2014 May 11];16(2):180–IN27. Available from: http://www.sciencedirect.com/science/article/pii/S1476558614800171]. Reprinted with permission under the terms of the Creative Commons Attribution License.
