Back to Search
Start Over
Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis
Microfluidic source-sink model reveals effects of biophysically distinct CXCL12 isoforms in breast cancer chemotaxis
- Source :
- Integr. Biol.. 6:564-576
- Publication Year :
- 2014
- Publisher :
- Oxford University Press (OUP), 2014.
-
Abstract
- Chemokines critically regulate chemotaxis in normal and pathologic states, but there is limited understanding of how multicellular interactions generate gradients needed for cell migration. Previous studies of chemotaxis of CXCR4+ cells toward chemokine CXCL12 suggest the requirement of cells expressing scavenger receptor CXCR7 in a source-sink system. We leveraged an established microfluidic device to discover that chemotaxis of CXCR4 cells toward distinct isoforms of CXCL12 required CXCR7 scavenging only under conditions with higher than optimal levels of CXCL12. Chemotaxis toward CXCL12-β and -γ isoforms, which have greater binding to extracellular molecules and have been largely overlooked, was less dependent on CXCR7 than the more commonly studied CXCL12-α. Chemotaxis of CXCR4+ cells toward even low levels of CXCL12-γ and CXCL12-β still occurred during treatment with a FDA-approved inhibitor of CXCR4. We also detected CXCL12-γ only in breast cancers from patients with advanced disease. Physiological gradient formation within the device facilitated interrogation of key differences in chemotaxis among CXCL12 isoforms and suggests CXCL12-γ as a biomarker for metastatic cancer.
- Subjects :
- Gene isoform
Benzylamines
Chemokine
Microfluidics
Biophysics
Breast Neoplasms
Cyclams
Biochemistry
CXCR4
Article
03 medical and health sciences
0302 clinical medicine
Heterocyclic Compounds
Cell Line, Tumor
Extracellular
medicine
Animals
Humans
Protein Isoforms
Microscopy, Phase-Contrast
RNA, Neoplasm
Scavenger receptor
030304 developmental biology
Receptors, CXCR
0303 health sciences
biology
Reverse Transcriptase Polymerase Chain Reaction
Chemotaxis
Cancer
Cell migration
medicine.disease
Chemokine CXCL12
biological factors
Cell biology
Mice, Inbred C57BL
Microscopy, Fluorescence
030220 oncology & carcinogenesis
embryonic structures
biology.protein
Female
biological phenomena, cell phenomena, and immunity
Subjects
Details
- ISSN :
- 17579708 and 17579694
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Integr. Biol.
- Accession number :
- edsair.doi.dedup.....96fd09383ab4edd296e9135f14aa67dc
- Full Text :
- https://doi.org/10.1039/c4ib00015c