Abstract
Pancreatic cancer is characterized by a 5-year survival rate of 3%, in part due to inadequate detection methods. The small size of peptides offers advantages regarding molecular targeting. Thus, peptides may be used in detection of pancreatic cancer. Here, peptides that target pancreatic cancer cells were selected using phage display technology using a 15-mer fUSE5 library. Phage were pre-cleared against immortalized pancreatic cells (hTERT-HPNE), followed by selections against pancreatic cancer (Mia Paca-2) cells. Next-generation sequencing identified two peptides, MCA1 and MCA2, with a Log2 fold change (Mia Paca-2/ hTERT-HPNE) >1.5. Modified ELISA and fluorescent microscopy showed that both peptides bound significantly higher to Mia Paca-2 cells, and not to hTERT-HPNE, embryonic kidney (HEK 293), ovarian (SKOV-3) and prostate cancer (LNCaP) cell lines. Further characterization of MCA1 and MCA2 revealed EC50 values of 16.11 µM (95% CI [9.69, 26.31 µM]) and 97.01 µM (95% CI [58.64, 166.30 µM]), respectively. Based on these results, MCA1 was selected for further studies. A competitive dose response assay demonstrated specific binding and an IC50 value of 2.15 µM (95% CI [1.28, 3.62 µM]). Taken together, this study suggests that MCA1 may be used as a pancreatic cancer targeting ligand for detection of the disease.
Highlights
Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer-related deaths in the United States [1]
The library was further subjected to a negative selection round against immortalized human pancreatic cells, which was followed by four rounds of positive selections against human pancreatic cancer cells (Mia Paca-2)
The results showed that MCA3 was previously identified in phage display selections against caveolin [35], and mouse zona pellucida [36], and was used as a negative control peptide in studies targeting cancer antigens [37,38]
Summary
Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer-related deaths in the United States [1]. One of the main hallmarks of pancreatic cancer is rapid tumor invasion and systemic dissemination throughout the body [2]. The aggressive metastatic progression combined with asymptomatic disease development and inadequate diagnostic methods lead to an average 5-year survival rate of approximately 3% [1,3]. Measurement of the levels of the serum carbohydrate (or cancer) antigen 19-9 (CA19-9) is currently in use for detection of pancreatic cancer [7,8,9]. This method is inadequate for early diagnosis due to low expression levels. Improved detection of pancreatic cancer is needed to enhance prognosis for patients
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