CNRS Enzyme and Cell Engineering Laboratory, Université de Technologie de Compiègne, Rue du Docteur Schweitzer, CS 60319, 60203 Compiègne Cedex, France.
The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
J Mater Chem B. 2022 Sep 15;10(35):6688-6697. doi: 10.1039/d2tb00680d.
Cadherins are cell-surface proteins that mediate cell-cell adhesion. By regulating their grip formation and strength, cadherins play a pivotal role during normal tissue morphogenesis and homeostasis of multicellular organisms. However, their dysfunction is associated with cell migration and proliferation, cancer progression and metastasis. The conserved amino acid sequence His-Ala-Val (HAV) in the extracellular domain of cadherins is implicated in cadherin-mediated adhesion and migration. Antagonists of cadherin adhesion such as monoclonal antibodies and small molecule inhibitors based on HAV peptides, are of high therapeutic value in cancer treatment. However, antibodies are not stable outside their natural environment and are expensive to produce, while peptides have certain limitations as a drug as they are prone to proteolysis. Herein, we propose as alternative, a synthetic antibody based on molecularly imprinted polymer nanogels (MIP-NGs) to target the HAV domain. The MIP-NGs are biocompatible, have high affinity for N-cadherin and inhibit cell adhesion and migration of human cervical adenocarcinoma (HeLa) cells, as demonstrated by cell aggregation and Matrigel invasion assays, respectively. The emergence of MIPs as therapeutics for fighting cancer is still in its infancy and this novel demonstration reinforces the fact that they have a rightful place in cancer treatment.
钙黏蛋白是一种细胞表面蛋白，介导细胞间的黏附。通过调节其附着形成和强度，钙黏蛋白在正常组织形态发生和多细胞生物的内稳态中发挥关键作用。然而，它们的功能障碍与细胞迁移和增殖、癌症进展和转移有关。钙黏蛋白细胞外结构域中的保守氨基酸序列 His-Ala-Val（HAV）参与钙黏蛋白介导的黏附和迁移。钙黏蛋白黏附的拮抗剂，如基于 HAV 肽的单克隆抗体和小分子抑制剂，在癌症治疗中具有很高的治疗价值。然而，抗体在其天然环境之外不稳定，生产成本高，而肽作为药物具有一定的局限性，因为它们容易被蛋白水解。在此，我们提出了一种基于分子印迹聚合物纳米凝胶（MIP-NGs）的合成抗体来靶向 HAV 结构域。MIP-NGs 具有生物相容性，对 N-钙黏蛋白具有高亲和力，并通过细胞聚集和 Matrigel 侵袭实验分别抑制人宫颈腺癌（HeLa）细胞的黏附和迁移。作为治疗癌症的药物，MIP 的出现仍处于起步阶段，这一新的研究结果证实了它们在癌症治疗中的合理地位。
