gms | German Medical Science

Introduction: Cilengitide (Cil), an inhibitor of integrins αvβ3 and αvβ5, is under investigation in clinical trials in head and neck squamous cell carcinoma (HNSCC). However, combinatory effects of Cil with Erbitux (E) on colony-formation (CF) of HNSCC on various extracellular matrix proteins were not investigated so far.

Methods: Biopsies of HNSCC were collagenase-digested and seeded into microtiter-plates coated with either collagen (C), fibronectin (F) or laminin (L) and grown for 3 days in the presence of 10 µM Cil ±66 µg/ml E in the FLAVINO-assay. Ethanol-fixed epithelial cells were stained by Cy2-labeled anti-cytokeratin-antibodies and fluorescent colonies counted.

Results: CF of HNSCC was highest on C followed by F and L. Suppressive effects of Cil on CF were ECM-dependent: On C, CF of 43 evaluable HNSCC was suppressed by Cil in 24 (55.8%), by E in 29 (67.4%), and by Cil+E in 35 (81.4%) cases. On F, CF was suppressed by Cil in 38 (86.4%), by E in 31 (70.4%), and by Cil+E in 37 (84.1%) of 44 evaluable HNSCC. CF on L was suppressed by Cil in 32 (82.0%), by E in 30 (76.9%), and by Cil+E in 33 (84.6%) of 39 evaluable HNSCC. While strength in suppression of CF by E was comparable on C, F and L (40.0%, 37.4%, and 35.5%), the median suppression by Cil and Cil+E differed remarkably and was lowest on C (23.1%; 50%) but higher on L (57.1%; 60.3%) and F (60.8%, and 70.0%) due to specific interference with ECM binding and CF.

Conclusion: Cil demonstrated ECM-dependent suppressive effects on tumor growth and in particular CF. Since the FLAVINO-assay indicates higher efficacy of E in presence of Cil in a large number of HNSCC, our investigations raise a rational to investigate the impact of both compounds on HNSCC further in clinical trials.

Support: The study was supported by Merck.

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