FIGURE 1.

Increased and poorer prognosis of integrin α6 in PDAC and the optimization of a peptide targeting integrin α6. A, According to the TCGA database, increased integrin α6 expression was observed in tumor tissues of PADC patients. B and C, Based on the GEPIA database, patients with higher integrin α6 expression in the tumor tissue showed a poorer prognosis for overall and disease‐free survival. D, The binding affinities of seven Ala‐mutated peptides were analyzed by ELISA. E, The in vivo blocking assays were performed via intravenous injection of 6 nmol of Cy5‐RWY together with 6 μmol of the unlabeled RWY peptide, or its scrambled peptide or a set of its alanine‐scanning mutant peptides into mice bearing Sw1990 tumors. The S5 peptide had the highest blocking effect on Cy5‐RWY. F and G, Sw1990 cells were incubated with Cy5‐RWY and Cy5‐S5 at 37°C for 30 min, and the integrin α6‐binding affinities of Cy5‐RWY and Cy5‐S5 were analyzed by flow cytometric analysis (F); the fluorescence intensity of the S5 group presented as relative (1.41 ± 0.03) fold over RWY, indicating a higher tumor cell‐binding ability of S5. H and I To further investigate the in vivo tumor‐binding ability of the S5 peptide, Cy5‐S5, Cy5‐RWY, and Cy5‐CG7C (negative control) were synthesized and used in NIRF. In the in vivo NIRF imaging of mice bearing subcutaneous Sw1990‐luciferase xenografts, Cy5‐S5 exhibited higher fluorescence intensity in tumor location (black arrow: the xenograft) (H); the fluorescence intensity of Cy5‐S5 presented as relative fold over RWY (2.64 ± 0.09) was significantly higher than that of Cy5‐RWY (1.00 ± 0.10, P = .000) (mean ± SD, ANOVA in (D) and (E) and Student's t‐test in (G) and (I) were used for statistical analysis. *P < .05, **P < .01, ***P < .001. NS, not significant)