title: Migration of breast cancer cell lines in response to pulmonary laminin 332.
abstract: Because tumor cell motility is a requirement for metastasis, we hypothesized that lung tissue harbors substances that induce tumor cell migration. MCF-7 breast carcinoma cells exposed to small airway epithelial cells and conditioned medium exhibited dose-dependent tumor cell migration. Among the extracellular matrix proteins in the conditioned medium identified by mass spectrometry, laminin 332 (LM332) had the greatest contribution to the migration of MCF-7 cells. Immunoblotting and immunohistochemistry for LM332-specific chains identified LM332 in the lung and in pulmonary epithelial cells. Antibodies to either LM332 or its integrin receptor inhibited MCF-7 motility, and knockdown of LM332 chains also reduced its migration-inducing activity. Taken together, these findings implicate LM332 as a component of lung tissue that can induce motility in breast carcinoma cells that have been transported to lung during metastasis. Earlier studies on LM332 in tumor progression have examined LM332 expression in tumor cells. This investigation, in comparison, provides evidence that the tumor promoting potential of LM332 may originate in the lung microenvironment rather than in tumor cells alone. Furthermore, this study provides evidence that the motility-inducing properties of the microenvironment can reside in epithelial cells. The findings raise the possibility that LM332 plays a role in the pulmonary metastases of breast carcinoma and may provide a target for antimetastasis therapy.
authors.affiliation: Department of Pathology, Keck School of Medicine, the University of Southern California, Los Angeles, California.|Department of Pathology, University of California, Irvine, California.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Carpenter
authors.affiliation: Department of Pathology, Keck School of Medicine, the University of Southern California, Los Angeles, California.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Sivadas
authors.affiliation: Department of Pathology, University of California, Irvine, California.
authors.forename: Spencer S
authors.initials: SS
authors.lastname: Hua
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University Hospital of Cologne, Cologne, Germany.
authors.forename: Cally
authors.initials: C
authors.lastname: Xiao
authors.affiliation: St. George's University, St. George, Grenada.
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Gutierrez
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, California.
authors.forename: Tuan
authors.initials: T
authors.lastname: Ngo
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, California.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Gershon
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000032:analysis; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D061986:MCF-7 Cells; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D000097794:Kalinin
keywords: Laminin 332; pulmonary epithelium; tumor cell migration; tumor microenvironment