A new obligate CXCL4-CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms

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Nesmelova, I., Ngyuen, K. T. P., Dreau, D., & Volkman, B. (2022). A new obligate CXCL4-CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms. Scientific Reports. https://doi.org/doi:10.1038/s41598-022-21651-0
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Description

Faculty, Chemokines form a family of proteins with critical roles in many biological processes in health and disease conditions, including cardiovascular, autoimmune diseases, infections, and cancer. Many chemokines engage in heterophilic interactions to form heterodimers, leading to synergistic activity enhancement or reduction dependent on the nature of heterodimer-forming chemokines. In mixtures, different chemokine species with diverse activities coexist in dynamic equilibrium, leading to the observation of their combined response in biological assays. To overcome this problem, we produced a non-dissociating CXCL4–CXCL12 chemokine heterodimer OHD4–12 as a new tool for studying the biological activities and mechanisms of chemokine heterodimers in biological environments. Using the OHD4–12, we show that the CXCL4–CXCL12 chemokine heterodimer inhibits the CXCL12-driven migration of triple-negative MDA-MB-231 breast cancer cells. We also show that the CXCL4–CXCL12 chemokine heterodimer binds and activates the CXCR4 receptor.

Details
Title

A new obligate CXCL4-CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms

Author(s)

Nesmelova, Irina
Ngyuen, Khanh T.P.
Dreau, Didier
Volkman, Brian

UNC Charlotte Affiliate Type

Faculty

Extent

1 online resource

Date Created

2022

Genre

articles

Resource Type

text

Abstract

Chemokines form a family of proteins with critical roles in many biological processes in health and disease conditions, including cardiovascular, autoimmune diseases, infections, and cancer. Many chemokines engage in heterophilic interactions to form heterodimers, leading to synergistic activity enhancement or reduction dependent on the nature of heterodimer-forming chemokines. In mixtures, different chemokine species with diverse activities coexist in dynamic equilibrium, leading to the observation of their combined response in biological assays. To overcome this problem, we produced a non-dissociating CXCL4–CXCL12 chemokine heterodimer OHD4–12 as a new tool for studying the biological activities and mechanisms of chemokine heterodimers in biological environments. Using the OHD4–12, we show that the CXCL4–CXCL12 chemokine heterodimer inhibits the CXCL12-driven migration of triple-negative MDA-MB-231 breast cancer cells. We also show that the CXCL4–CXCL12 chemokine heterodimer binds and activates the CXCR4 receptor.

Subjects--Topics

Chemokines
Proteins

Is Part Of

Scientific reports

Language

English

Published Version (Please cite this version)

doi:10.1038/s41598-022-21651-0

Publisher's Version

https://doi.org/10.1038/s41598-022-21651-0

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