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Lung-Derived Factors Mediate Breast Cancer Cell Migration through CD44 Receptor-Ligand Interactions in a Novel…

Escrito por Carla Brito Lopes


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.


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:]. Reprinted with permission under the terms of the Creative Commons Attribution License.

Sobre o autor

Carla Brito Lopes

Carla nasceu em Viana do Castelo em 1977. Licenciada em Anatomia Patológica, Citológica e Tanatológica pela Escola Superior de Tecnologia da Saúde em Lisboa. Concluiu a certificação em Laboratory Management pela ASCP (American Association of Clinical Pathology) em Setembro de 2016. Mestre em Genética Molecular e Biomedicina pela Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa. Trabalhou no Centro Hospitalar Lisboa Central entre 1998 e 2015, exercendo histopatologia e imunohistoquímica, sendo co-responsável pelo sector. Trabalha no Dr. Joaquim Chaves, Laboratório de Anatomia Patológica desde 2004 onde exerce funções de Coordenação Técnica e da Qualidade.