Motility induction in breast carcinoma by mammary epithelial laminin 332 (laminin 5)

Philip M. Carpenter, Anh V. Dao, Zahida S. Arain, Michelle K. Chang, Hoa P. Nguyen, Shehla Arain, Jessica Wang-Rodriguez, Soon Young Kwon, Sharon P. Wilczynski

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37 Citations (Scopus)

Abstract

Host interactions with tumor cells contribute to tumor progression by several means. This study was done to determine whether mammary epithelium could interact with breast carcinoma by producing substances capable of inducing motility in the cancer cells. Conditioned medium of immortalized 184A1 mammary epithelium collected in serum-free conditions induced dose-dependent motility in the MCF-7 breast carcinoma cell line by both a semiquantitative scattering assay and a Boyden chamber assay. Purification of the motility factor revealed that it was laminin 332 (formerly laminin 5) by mass spectroscopy. A Western blot of the 184A1 conditioned medium using a polyclonal antibody confirmed the presence of laminin 332 in the conditioned medium. Blockage of the motility with antibodies to the laminin 332 and its receptor components, α3 and β1 integrins, provided further evidence that tumor cell motility was caused by the laminin 332 in the conditioned medium. Invasion of MCF-7, BT-20, and MDA-MB-435S was induced by purified laminin 332 and 184A1 conditioned medium and blocked by an anti-α3 integrin antibody. Staining of carcinoma in situ from breast cancer specimens revealed that laminin 332 in the myoepithelium adjacent to the preinvasive cells provided a source of laminin 332 that could potentially encourage the earliest steps of stromal invasion. In metaplastic breast carcinomas, the presence of laminin 332-producing cells coexpressing α3 integrin and the greater metastatic potential of tumors with higher laminin 332 levels suggest that laminin 332 expression is associated with aggressive features in these human breast cancers.

Original languageEnglish
Pages (from-to)462-475
Number of pages14
JournalMolecular Cancer Research
Volume7
Issue number4
DOIs
Publication statusPublished - 2009 Apr 1

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Carpenter, P. M., Dao, A. V., Arain, Z. S., Chang, M. K., Nguyen, H. P., Arain, S., Wang-Rodriguez, J., Kwon, S. Y., & Wilczynski, S. P. (2009). Motility induction in breast carcinoma by mammary epithelial laminin 332 (laminin 5). Molecular Cancer Research, 7(4), 462-475. https://doi.org/10.1158/1541-7786.MCR-08-0148