Collodet Caterina, Blust Kelly, Gkouma Savvini, Ståhl Emmy, Chen Xinsong, Hartman Johan, Hedhammar My
Division of Protein Technology School of Biotechnology, KTH Royal Institute of Technology Stockholm Sweden.
Department of Oncology-Pathology Karolinska Institutet Stockholm Sweden.
Bioeng Transl Med. 2023 May 11;8(5):e10537. doi: 10.1002/btm2.10537. eCollection 2023 Sep.
Traditional cancer models rely on 2D cell cultures or 3D spheroids, which fail to recapitulate cell-extracellular matrix (ECM) interactions, a key element of tumor development. Existing hydrogel-based 3D alternatives lack mechanical support for cell growth and often suffer from low reproducibility. Here we report a novel strategy to make 3D models of breast cancer using a tissue-like, well-defined network environment based on recombinant spider silk, functionalized with a cell adhesion motif from fibronectin (FN-silk). With this approach, the canonical cancer cells SK-BR-3, MCF-7, and MDA-MB-231, maintain their characteristic expression of markers (i.e., ERα, HER2, and PGR) while developing distinct morphology. Transcriptomic analyses demonstrate how culture in the FN-silk networks modulates the biological processes of cell adhesion and migration while affecting physiological events involved in malignancy, such as inflammation, remodeling of the ECM, and resistance to anticancer drugs. Finally, we show that integration in FN-silk networks promotes the viability of cells obtained from the superficial scraping of patients' breast tumors.
传统的癌症模型依赖于二维细胞培养或三维球体，而这些无法重现细胞与细胞外基质（ECM）的相互作用，这是肿瘤发展的关键要素。现有的基于水凝胶的三维替代物缺乏对细胞生长的机械支持，并且常常存在重现性低的问题。在此，我们报告一种新颖的策略，即使用基于重组蜘蛛丝的组织样、明确的网络环境来制作乳腺癌的三维模型，该环境用来自纤连蛋白的细胞粘附基序（FN-丝）进行功能化修饰。通过这种方法，典型癌细胞SK-BR-3、MCF-7和MDA-MB-231在形成独特形态的同时，维持其标志物（即ERα、HER2和PGR）的特征性表达。转录组分析表明，在FN-丝网络中培养如何调节细胞粘附和迁移的生物学过程，同时影响与恶性肿瘤相关的生理事件，如炎症、ECM重塑和抗癌药物耐药性。最后，我们表明整合到FN-丝网络中可促进从患者乳腺肿瘤表面刮取获得的细胞的活力。
