Work

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

Year: 2022

Type: article

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 OHD4–12as 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.

Source: Scientific Reports

DOI: 10.1038/s41598-022-21651-0

Authors: Khanh T.P. Nguyen, Brian Volkman, Didier Dréau, Irina V. Nesmelova

Institutions: University of North Carolina at Charlotte, Medical College of Wisconsin

Language: English

Topic: Chemokine receptors and signaling

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,190