Head and neck cancers (HNCs) account for a small percentage of all cancers in the United States, but their localization complicates surgical treatment. Therefore, chemotherapy is the most viable treatment option. In this study, the hypopharyngeal carcinoma cell line FaDu was treated with collagen/cell-penetrating hybrid peptides that have a potential to be effective drug-carriers. Confocal microscopy shows that one of the hybrid peptides, FL8V1, is able to function as an effective drug carrier: it is internalized by FaDu via endosomal uptake and manages to escape from the endosome before it matures into a lysosome.
In addition, it was observed an unusual localization of hybrid peptides at the cell surface, that was not observed in previous experiments involving different malignant and healthy cells. Initially, it was hypothesized that the studied peptides interact with the tight junctions of the FaDu cell membrane. However, colocalization experiments performed with one of the hybrid peptides and the tight junction protein JAM-A in FaDu cells showed that they did not colocalize. Subsequently, the salt wash of FaDu cells was performed to determine if the interaction of peptide with the FaDu cell surface was specific or non-specific. These experiments showed that the interactions were non-specific. Compared to other cell lines studied in the past, FaDu is the only cell line that exhibits this behavior, therefore it is speculated that the FaDu cell membrane is uniquely polarized in comparison to other malignant cells. More studies are required to assess the reason for the hybrid peptide preconcentration at the FaDu cell surface. The differences in the behavior between FaDu and other malignant cells may lead to clinical applications in the treatment of HNCs in the future.
|Commitee:||Bhandari, Deepali, Weers, Paul|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 58/05M(E), Masters Abstracts International|
|Keywords:||CPP, FaDu, HNC, HNSCC, Hybrid peptide|
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