Hematology, Transfusion and Cell Therapy (Apr 2024)
INFLUENCE OF A CONVENTIONAL CHELATOR-MODIFIED ANTI-INTEGRIN PEPTIDE ON PROLIFERATION AND MIGRATION OF HEAD AND NECK CANCER CELLS
Abstract
Introduction/Justification: Head and neck squamous cell carcinoma (HNSCC) represents a serious health problem worldwide. Approximately 75% of patients with HNSCC have locally advanced disease at diagnosis, and the therapy for those cases involves chemoradiation or induction chemotherapy, in which cisplatin is included despite of its substantial side effects. FAPESP-founded “Cancer Innovation Center with Emphasis on Metals and Theranostics” (CancerThera) is dedicated to the development of new metallopharmaceuticals and radiopharmaceuticals for tumor diagnosis and treatment. Among these developments, an anti-integrin peptide modified by a conventional spacer (C6) and chelator (DOTA) was evaluated as a potential treatment of HNSCC. Overexpressed in HNC, integrins are transmembrane proteins that play essential roles in cell proliferation and migration. Therefore, integrin inhibition may be a potential targeted therapy for HNC patients. Objectives: The study aimed to evaluate the effects of the DOTA-C6-anti-integrin peptide on HNSCC cell lines proliferation and migration, as an initial step for HNSCC theranostic development. Materials and Methods: The anti-proliferative activity of the DOTA-C6-anti-integrin peptide (0.01nM - 100µM) was assessed against FaDu and SCC-25 cells by considering the cell amounts at baseline and 48h after exposure (two untreated control groups). All cells were fixed with 50% trichloroacetic acid and stained with sulforhodamine B. Spectrophotometric absorbance was performed at 540nm in a microplate reader. Cell migration was assessed in FaDu cells and FaDu cells treated with the DOTA-C6-anti-integrin peptide (1, 10, and 100µM) using the wound-healing assay. Wound cells were photographed immediately (0h) and after 16h, 24h, and 40h. Images were analyzed by the ImageJ software (National Institutes of Health). For statistical analysis, samples did assume normal distribution in Shapiro-Wilk's test, thus we used t test to compare the groups using SPSS 21 software (SPSS Incorporation). Results: At the tested concentration range, the DOTA-C6-anti-integrin peptide did not affect proliferation of FaDu or SCC-25 cells. In FaDu cells, the DOTA-C6-anti-integrin peptide significantly (p < 0.05) inhibited migration in comparison to untreated cells, independent on sample concentration (1, 10, and 100µM) or time exposure (16, 24, or 40 h). Conclusion: Despite the lack of anti-proliferative effect, the DOTA-C6-anti-integrin peptide inhibited migration in FaDu cells. As cell migration is an important process in HNSCC progression, our data present preliminary evidence that the DOTA-C6-anti-integrin may be used in development of theranostic agents for HNSCC. Acknowledgements: The study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNP #429463/2018-9), Fundação de Apoio ao Ensino e à Pesquisa do Estado de São Paulo (FAPESP #2023/09738-4, FAPESP #2023/012810-9, Cancer Theranostics Innovation Center, (CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375).
