[In-vivo screening and characterization of peptides specific for vasculature of gastric cancer].

AIM

To screen in vivo from a phage-displayed peptide library polypeptide fragments specific binding to vascular endothelial cells of gastric cancer xenografts, so as to provide for anti-angiogenesis therapy of tumor.

METHODS

Immunosupressed mice models for human gastric cancer xeno-grafts were established by subrenal capsular assay (SR-CA). The 12-peptide library was panned through 4 rounds. Phages were recovered and titrated from tumor xenografts and control tissue (brain). The distribution of phage were detected in transplanted tumor tissues by immunohistochemical staining.

RESULTS

Phage homing to gastric cancer xenografts were enriched through four rounds of panning,being 3.4-fold of that recovered from brain tissue. Peptide sequences were characterized for randomly picked-upclones and the peptide sequence YESIRIGVAPSQ appeared most frequently. Immunohistochemical staining for the homing phage revealed a specific vascular endothelial cell localization in gastric cancer xenografts 5 min after injection of the enriched phages. When the specific phage individually test-ed, the phage recovered from gastric cancer xenografts were as 4. 2 times as those from control tissue ( brain) , as 4.9 times as those from lung, as 5.4 times as those from heart.

CONCLUSION

The tumor-specific homing peptides may provide a effective tool for targeting tumor vasculature in anti-angiogenesis therapy of cancer. The in vivo selection technique in this study was feasible and applicable to screening peptides homing to vascular endothelial cells.