Molecular mechanism and inhibitor development of platelet-dependent tumor growth progression in hematogenous metastasis

本研究的目的是阐明通过与血小板相互作用而激活的癌细胞中的信号转导途径，并开发针对这些信号转导途径的抑制剂。我发现，血小板和肉瘤细胞的直接相互作用通过促进肿瘤生长和肿瘤耐药而促进肿瘤的恶性发展，并确定PI3K-Akt通路是导致血小板介导的肿瘤恶性的关键信号转导途径。此外，肉瘤细胞诱导的血小板聚集依赖于血小板聚集诱导因子Aggrus，这表明抗Aggrus中和抗体可用作某些类型癌症的血行转移抑制因子。

The purpose of this study is to clarify the signal transduction pathways in cancer cells activated by interaction with platelets and to develop inhibitors against these signaling pathways. I found that direct interaction of platelets and sarcoma cells contributes to tumor malignancy by enhancing both tumor growth and tumor drug resistance, and identified PI3K-Akt pathway as a key signal transduction pathway which causes platelet-mediated tumor malignancy. Furthermore, sarcoma cell-induced platelet aggregation is dependent on platelet-aggregation inducing factor Aggrus, suggesting that anti-Aggrus neutralizing antibodies would be useful as hematogenous metastasis inhibitors against some types of cancers