靶向药物以其高效低毒的优势，在结肠癌治疗中发挥重要作用。P-选择素（P-selectin）是重要的粘附分子，目前尚无以其为靶点的药物用于临床。我们前期研究证实，P-selectin通过P-selectin-Talin1-integrin信号介导血小板与结肠癌细胞粘附，促进结肠癌生长。由此我们研发了可溶性P-选择素重组蛋白（P-sel-Fc），并证实其阻断血小板粘附抑制肿瘤侵袭转移。但P-sel-Fc对结肠癌侵袭转移的作用及具体机制尚不明确。我们已结题国家自然基金研究表明结肠癌干细胞是其侵袭转移的元凶，由此推测P-selectin介导血小板与结肠癌干细胞"对话"而促进其侵袭转移。本项目中，我们将利用基因工程小鼠模型和分子生物学体系，进一步证实P-sel-Fc抑制结肠癌侵袭转移的效果，明确其分子靶向机制；为以P-选择素为靶点阻断血小板和结肠癌干细胞"对话"的抗肿瘤药物开发作出开创性的工作。

Targeted drugs bring a gleam of hope with low toxicity and high selectivity for the therapy of colon cancer. P-selectin (CD62P) is a member of the selectin family of cell adhesion molecules, still no drugs targeted P-selectin are used in clinic up to now. In our prophase study, we confirmed P-selectin, mediates the adhesion between platelets and colon cancer cell by regulating P-selectin-Talin1-integrin signaling pathway, thus promote the growth and invasion of colon cancer. Accordingly, we developed recombinant soluble P-selectin protein (P-sel-Fc), and confirmed that P-sel-Fc inhibit tumor invasion and metastasis, and it did not lead to bleed. Our study in the finished NSFC project also indicated that colon cancer stem cell is the fountain of tumor growth, invasion and metastasis. Thereby, we presume that there is interaction between colon cancer stem cells and platelets, and P-selectin is their mediator. In the current project, we will further validate the inhibitory effect of P-sel-Fc on the tumor invasion and metastasis of colon cancer; reveal the crosstalk between colon cancer stem cells and platelets; and identify the molecule mechanism of P-sel-Fc blocking P-selectin-Talin1-integrin signaling pathway. By targeting this platelet-colon cancer stem cell crosstalk, soluble P-selectin protein may afford significant advantages over currently available therapeutics for treating colon cancer.