Protection of the glycocalyx reduces myeloid leukocyte trafficking and tumor progression in experimental HNSCC

Introduction Myeloid leukocytes have been implicated in initiation, progression, and metastasis of malignant tumors including head and neck squamous cell carcinoma (HNSCC). How these immune cells reach the neoplastic lesions, however, is poorly understood. The glycocalyx (GCX) is a polysaccharide- and glycoprotein-rich layer on the surface of eukaryotic and prokaryotic cells, which regulates cell-cell interactions. The role of the GCX for myeloid leukocyte trafficking and progression in HNSCC remains largely obscure.

Methods The endothelial glycocalyx (eGCX) in tumor microvessels was quantitatively analyzed in experimental mouse HNSCC (cell line SCC VII) by wheat germ agglutinin and in vivo multiphoton microscopy. In the same model, recruitment of myeloid leukocytes, extravasation of FITC-dextran as well as tumor growth was examined.

Results Microvessels in HNSCC exhibit a significantly reduced eGCX as compared to healthy tissue. This status is associated with an increased intravascular accumulation of neutrophils and classical monocytes as well as with microvascular hyperpermeability. Pharmacological protection of the GCX leads to a significant reduction of myeloid immune cell recruitment and microvascular permeability in tumors as well as to a significantly decreased tumor growth.

Conclusions The GCX critically regulates trafficking of myeloid leukocytes and microvascular permeability as well as tumor progression in experimental HNSCC. Consequently, pharmacological protection of the GCX might emerge as promising therapeutic target in head and neck immuno-oncology.

Poster-PDF A-1556.PDF

Conflict of Interest Diese Studie wird durch den Sonderforschungsbereich (SFB) 914 der Deutschen Forschungsgemeinschaft (DFG) unterstützt.

Publication History

Article published online:
10 June 2020