Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Chemokines and their receptors are crucial in oral cancer development.
• The atypical chemokine receptor ACKR2 scavenges CC chemokines, influencing their availability at tumor sites.
• The specific role of ACKR2 in oral carcinogenesis remains largely unexplored.

Purpose of the Study:

• To investigate the role of ACKR2 in chemically induced oral carcinogenesis.
• To analyze the impact of ACKR2 deficiency on tumor development and associated molecular changes.

Main Methods:

• Oral carcinogenesis was induced in wild-type (WT) and ACKR2-deficient (ACKR2^-/-) mice using 4-nitroquinoline-1-oxide (4NQO).
• Tongue tissues were analyzed for macro/microscopic changes, and expression of ACKRs, CC chemokines, inflammatory cytokines, angiogenic factors, adhesion molecules, and extracellular matrix components was evaluated.

Main Results:

• ACKR2 expression increased in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice.
• No significant differences in ACKR1, ACKR3, or ACKR4 mRNA expression were observed between WT and ACKR2^-/- mice.
• Higher expression of CCL2, IL-6, and IL-17 was noted in ACKR2^-/- mice, while other factors showed similar increases in both groups.
• Clinical and histopathological analyses revealed no differences in inflammatory cell recruitment or SCC incidence between WT and ACKR2^-/- mice.

Conclusions:

• ACKR2 expression influences the inflammatory tumor microenvironment.
• The absence of ACKR2 does not impede chemically induced oral carcinogenesis.
• ACKR2 may not be a critical factor in the progression of oral cancer.