Khine Kyaw Oo1, Thanpawee Kamolhan2, Anish Soni3, Suyanee Thongchot2,4, Chalermchai Mitrpant5, Pornchai O-Charoenrat6,7, Chanitra Thuwajit2, Peti Thuwajit8. 1. Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. 2. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. 3. Bachelor of Science Program in Biological Science (Biomedical Science), Mahidol University International College, Mahidol University, Nakhon Pathom, 73170, Thailand. 4. Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. 5. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. 6. Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. 7. Breast Center, Medpark Hospital, Bangkok, 10110, Thailand. 8. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand. peti.thu@mahidol.edu.
Abstract
BACKGROUND: Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells. METHODS: A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data. RESULTS: The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data. CONCLUSIONS: This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.
BACKGROUND: Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PNpeptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells. METHODS: A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PNpeptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data. RESULTS: The results showed that a candidate anti-PNpeptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PNpeptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PNpeptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data. CONCLUSIONS: This finding supports that anti-PNpeptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.
Authors: Désirée Gül; Andrea Schweitzer; Aya Khamis; Shirley K Knauer; Guo-Bin Ding; Laura Freudelsperger; Ioannis Karampinis; Sebastian Strieth; Jan Hagemann; Roland H Stauber Journal: Cancers (Basel) Date: 2022-05-09 Impact factor: 6.575
Authors: Sun Young Jang; Jinjoo Kim; Jung Tak Park; Catherine Y Liu; Bobby S Korn; Don O Kikkawa; Eun Jig Lee; Jin Sook Yoon Journal: Front Endocrinol (Lausanne) Date: 2022-05-30 Impact factor: 6.055