A potential peptide vector that allows targeted delivery of a desired fusion protein into the human breast cancer cell line MDA-MB-231.
Effective control of breast cancer has been primarily hampered by a lack of tumor specificity in treatments. One potential way to improve targeting specificity is to develop novel vectors that specifically bind to and are internalized by tumor cells. Through a phage display library, an 11-L-amino acid peptide, PI (sequence, CASPSGALRSC), was selected. PI was labeled with fluorescein isothiocyanate (FITC) and named PI-FITC. Subsequently, the specific affinity of PI-FITC to MDA-MB-231 human breast cancer cells and other cancer cell lines was observed by confocal microscopy. Our previous study established that PI-FITC also shows affinity to Calu-1 human lung carcinoma cells and major histocompatibility complex class I antigen molecules; therefore, the cytomembrane proteins of the cell lines were analyzed to determine those that were common to the two cell lines and may be associated with transmembrane transduction. To further test the delivery ability of PI to MDA-MB-231 cells, PI-glutathione-S-transferase (GST) was constructed and the internalization of this fusion protein was visualized by immunofluorescence microscopy. The results revealed that PI exhibited specific affinity to MDA-MB-231 cells. Use of membrane transport inhibitors indicated that macropinocytosis and caveolin-mediated endocytosis may be involved in the endocytosis of PI. In addition, 11 membrane proteins common to MDA-MB-231 and Calu-1 may be associated with transmembrane transduction. In summary, PI was able to deliver PI-GST into MDA-MB-231 cells. Thus, PI could be modified to be a potential vector, and may contribute to the development of targeted therapeutic strategies for breast cancer.
Department of Internal Medicine Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Wei Qing
WQ
Liu
Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Jun
J
Yang
Department of Internal Medicine Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Min
M
Hong
Department of Internal Medicine Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Chang E
CE
Gao
Department of Internal Medicine Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China; Department of Internal Medicine Oncology, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650106, P.R. China.
Jian
J
Dong
MDA-MB-231 cell line; breast cancer; fusion protein delivery; peptide; transmembrane transduction; tumor targeting therapy; vector