The SDF1-CXCR4-axis in HPV-positive and HPV-negative HNSCC

Introduction:

Cancer stem cells (CSCs) are discussed to be a reason for insufficient therapy response in head and neck squamous cell carcinoma (HNSCC). Stromal cell-derived factor-1α (SDF-1α) and its receptor CXCR4 are important parts of the messenger system between CSCs and their protective niches. In order to encounter a better understanding of the superior survival rate of HPV+ HNSCCs, we studied the effect of SDF-1α on HPV+/HPV- SCC cell lines.

Methods:

An HPV+ (CERV196) and two HPV- (UM-SCC11A and UM-SCC14C) SCC cell lines were stained immunohistochemically for CD44 and CXCR4. The proliferation of the cells after incubation with different concentrations of SDF-1α was measured by an Alamar Blue® proliferation assay on four consecutive days. Using a Transwell migration assay we analyzed the migration of cells towards SDF-1α after 24h. Podia formation after incubation with SDF-1α for 24h was evaluated via light microscopy.

Results:

We verified the expression of CD44 and CXCR4 in all three cell lines. Under the influence of SDF-1α, HPV- SCCs formed significantly more podia and significantly more cells migrated towards SDF-1α, compared to negative controls. HPV+ SCCs showed no significant change of morphology or migration when SDF-1α was added. The proliferation of both HPV+ and HPV- SCCs was basically unchanged after treatment with SDF-1α.

Conclusion:

Our results indicate an impaired response of HPV+ SCCs to SDF-1α, which might lead to an altered communication between CSCs and their niche. These findings could contribute to the so far unsolved issue of a superior prognosis of HPV+ HNSCCs.

Publication History

Publication Date:
18 April 2018 (online)