title: Secretome identification of immune cell factors mediating metastatic cell homing.
abstract: Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting secretomics and TRanscriptional Activity CEll aRray (TRACER) data to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of homing. Metastatic breast cancer mouse models were used to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased in D-SCM relative to control media. Our D-SCM secretome analysis yielded 144 secreted factor candidates that contribute to increased metastatic cell activity. The functional mediators of homing were identified using MetaCore software to determine interactions between the immune cell secretome and the TRACER-identified active transcription factors within metastatic cells. Among the 5 candidate homing factors identified, haptoglobin was selected and validated in vitro and in vivo as a key mediator of homing. Our studies demonstrate a novel systems biology approach to identify functional signaling factors associated with a cellular phenotype, which provides an enabling tool that complements large-scale protein identification provided by proteomics.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.|Simpson Querrey Institute for Bionanotechnology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Aguado
authors.affiliation: Interdepartmental Biological Sciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jia J
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Samira M
authors.initials: SM
authors.lastname: Azarin
authors.affiliation: Proteomics Core Facility, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Nanavati
authors.affiliation: Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL 35487, USA.
authors.forename: Shreyas S
authors.initials: SS
authors.lastname: Rao
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.
authors.forename: Grace G
authors.initials: GG
authors.lastname: Bushnell
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Chaitanya B
authors.initials: CB
authors.lastname: Medicherla
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.|Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48105, USA.|Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000276:immunology; D009362:Neoplasm Metastasis; D019899:Paracrine Communication / Q000235:genetics* / Q000276:immunology; D040901:Proteomics; D015398:Signal Transduction / Q000235:genetics; D049490:Systems Biology
chemical_list: D007155:Immunologic Factors