Proteomics

Dataset Information

72

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 together secretomics and a TRanscriptional Activity CEll aRray (TRACER) to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of metastatic cell homing. Splenocytes from orthotopic mouse models of breast cancer were isolated 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 when cultured with D-SCM compared to healthy SCM (H-SCM) and unconditioned media controls. Our secretome analysis of D-SCM yielded secreted factor candidates that contribute to increased metastatic cell activity. In parallel, we identified active TFs within metastatic cells in response to the secreted factors using TRACER. We connected both data sets using MetaCore software to determine interactions between immune cell secreted factors and active metastatic cell TFs to narrow down functional secreted factor candidates that mediate metastatic cell homing. Haptoglobin was among the list of secreted factors and was validated in vitro as a key mediator of metastatic cell recruitment. Furthermore, we designed an implantable poly(lactide-co-glycolide) biomaterial scaffold as a mimic of the pre-metastatic niche to slowly release haptoglobin and demonstrate increased homing of metastatic cells to the scaffold in vivo. Taken together, our studies demonstrate a novel systems biology technique to identify functional paracrine signaling factors, which were validated to reveal mediators of metastatic cell homing.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus musculus  

TISSUE(S): Spleen

DISEASE(S): Not Available

SUBMITTER: Dhaval Nanavati  

LAB HEAD: Lonnie D. Shea, Ph.D

PROVIDER: PXD002051 | Pride | 2015-12-17

REPOSITORIES: Pride

Dataset's files

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08132013_BA_LS_01.msf Msf
08132013_BA_LS_01.raw Raw
08132013_BA_LS_02.msf Msf
08132013_BA_LS_02.raw Raw
08132013_BA_LS_03.msf Msf
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Publications

Secretome identification of immune cell factors mediating metastatic cell homing.

Aguado Brian A BA   Wu Jia J JJ   Azarin Samira M SM   Nanavati Dhaval D   Rao Shreyas S SS   Bushnell Grace G GG   Medicherla Chaitanya B CB   Shea Lonnie D LD  

Scientific reports 20151204


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.  ...[more]

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