The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, , 1 Discovery Drive, Rensselaer, NY, USA.
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, , 1 Discovery Drive, Rensselaer, NY, USA.
Cancer Treat Res Commun. 2021;28:100395. doi: 10.1016/j.ctarc.2021.100395. Epub 2021 May 13.
Integrins are a family of heterodimeric plasma membrane glycoproteins, which regulate tumor growth, angiogenesis, migration, and metastasis. Integrin αvβ3 has been recognized as a putative target for the treatment of several cancers. Thus, the characterization of αvβ3 distribution in different human tumors is of substantial interest in tumor targeting and its suppression. In this study we evaluated the expression of integrin αvβ3 in different cancer types to define the expression pattern in cancer model. Furthermore, we investigated the effect of novel αvβ3 antagonist Diaminopropane Tetraiodothyroacetic acid conjugated to poly (lactic-co-glycolic acid) polymer and its nanoformulated form (NDAT), on different cancer cell lines both in vitro and in xenografts. In vitro, NDAT downregulated αv and β3 monomer expression. In vivo in tumor xenografts, similarly, NDAT downregulated αv and β3. Distinct reduction in tumor weight and viability was observed in glioblastoma xenografts treated with NDAT. Furthermore, NDAT was safe and tolerable in mice treated with high doses. In conclusion, NDAT is an effective and safe inhibitor of integrin αvβ3 expression in various cancer types, which indicates its impact on the targetability and suppression of αvβ3-associated tumor functions.
整合素是一种异二聚体的质膜糖蛋白家族，可调节肿瘤生长、血管生成、迁移和转移。整合素αvβ3 已被认为是治疗多种癌症的潜在靶点。因此，在肿瘤靶向和抑制中，研究不同人类肿瘤中 αvβ3 的分布具有重要意义。在这项研究中，我们评估了整合素 αvβ3 在不同癌症类型中的表达，以确定其在癌症模型中的表达模式。此外，我们研究了新型整合素 αvβ3 拮抗剂二氨基丙基四碘甲状腺原氨酸与聚（乳酸-共-乙醇酸）聚合物及其纳米制剂（NDAT）对不同癌症细胞系的体外和异种移植的影响。体外实验中，NDAT 下调了 αv 和 β3 单体的表达。在体内肿瘤异种移植中，NDAT 也下调了 αv 和 β3。用 NDAT 治疗神经胶质瘤异种移植瘤，可明显降低肿瘤重量和活力。此外，在接受高剂量治疗的小鼠中，NDAT 安全且耐受良好。总之，NDAT 是一种有效且安全的整合素 αvβ3 抑制剂，可影响靶向性和抑制与 αvβ3 相关的肿瘤功能。
