Department of Chemistry, Western Illinois University, 1 University Circle, Macomb, IL 61455, USA.
Department of Biological Sciences, Western Illinois University, 1 University Circle, Macomb, IL 61455, USA.
Biomolecules. 2020 May 5;10(5):714. doi: 10.3390/biom10050714.
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 EC 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 IC 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.
胰腺癌的 5 年生存率仅为 3%，部分原因是检测方法不足。肽的小尺寸在分子靶向方面具有优势。因此，肽可用于胰腺癌的检测。本研究使用 15 肽 fUSE5 文库，通过噬菌体展示技术选择靶向胰腺癌细胞的肽。噬菌体首先用永生化胰腺细胞（hTERT-HPNE）预清除，然后针对胰腺癌细胞（Mia Paca-2）进行选择。下一代测序鉴定出两种肽，MCA1 和 MCA2，其 Log2 倍数变化（Mia Paca-2/hTERT-HPNE）>1.5。改良 ELISA 和荧光显微镜显示，两种肽与 Mia Paca-2 细胞的结合显著更高，而与 hTERT-HPNE、胚胎肾（HEK 293）、卵巢（SKOV-3）和前列腺癌细胞（LNCaP）系不结合。进一步表征 MCA1 和 MCA2 显示 EC 值分别为 16.11µM（95%CI [9.69，26.31µM]）和 97.01µM（95%CI [58.64，166.30µM]）。基于这些结果，选择 MCA1 进行进一步研究。竞争性剂量反应测定表明具有特异性结合，IC 值为 2.15µM（95%CI [1.28，3.62µM]）。综上所述，本研究表明 MCA1 可用作胰腺癌的靶向配体，用于该疾病的检测。
