通过胶原微纤维在 3D 结直肠癌基质组织中促进生物相似性:复制机械特性和癌症干细胞标记。
Promoting Biological Similarity by Collagen Microfibers in 3D Colorectal Cancer-Stromal Tissue: Replicating Mechanical Properties and Cancer Stem Cell Markers.
发表日期:2024 Jul 05
作者:
Naoko Sasaki, Yoshiya Asano, Yukiko Sorayama, Chihiro Kamimura, Shiro Kitano, Shinji Irie, Ryohei Katayama, Hiroshi Shimoda, Michiya Matsusaki
来源:
Stem Cell Research & Therapy
摘要:
癌组织的细胞外基质(ECM)富含致密胶原蛋白,有助于这些组织的硬化。据报道,硬度增加可促进癌细胞增殖、侵袭、转移并阻止药物输送。在体外复制癌症组织的结构和机械特性对于开发针对这些特性的癌症治疗药物至关重要。在这项研究中,我们使用结直肠癌细胞系作为模型,重建了癌症组织的特定特征,例如胶原蛋白密度和高弹性模量。使用我们的原始材料胶原微纤维 (CMF) 和构建的三维 (3D) 癌基质组织模型,我们成功复制了与体内条件高度相似的 ECM。此外,我们的研究表明,与传统的二维细胞培养物相比,3D 癌症基质组织模型中表达的癌症干细胞标记物更能模拟体内条件。我们还发现 CMF 可能会影响癌细胞表达这些标记物的方式。我们基于 3D CMF 的模型有望增强我们对结直肠癌的理解并推进治疗方法。意义陈述:再现癌症组织的胶原蛋白含量和硬度对于理解癌症的特性和推进抗癌药物的开发至关重要。尽管如此,使用胶原蛋白作为支架材料仍然面临着挑战,因为它的溶解性差,阻碍了癌症微环境的复制。在这项研究中,我们利用一种称为胶原微纤维 (CMF) 的专有材料,成功地重建了癌症组织特异性特征,例如三维 (3D) 结直肠癌基质组织中的胶原密度、硬度和癌症干细胞标记物的表达)。 CMF 被证明是复制癌症基质组织的理想支架材料,这些用 CMF 构建的 3D 组织有望有助于我们对癌症的理解和治疗药物的开发。版权所有 © 2024。由 Elsevier Ltd 出版。
The extracellular matrix (ECM) of cancer tissues is rich in dense collagen, contributing to the stiffening of these tissues. Increased stiffness has been reported to promote cancer cell proliferation, invasion, metastasis, and prevent drug delivery. Replicating the structure and mechanical properties of cancer tissue in vitro is essential for developing cancer treatment drugs that target these properties. In this study, we recreated specific characteristics of cancer tissue, such as collagen density and high elastic modulus, using a colorectal cancer cell line as a model. Using our original material, collagen microfibers (CMFs), and a constructed three-dimensional (3D) cancer-stromal tissue model, we successfully reproduced an ECM highly similar to in vivo conditions. Furthermore, our research demonstrated that cancer stem cell markers expressed in the 3D cancer-stromal tissue model more closely mimic in vivo conditions than traditional two-dimensional cell cultures. We also found that CMFs might affect an impact on how cancer cells express these markers. Our 3D CMF-based model holds promise for enhancing our understanding of colorectal cancer and advancing therapeutic approaches. STATEMENT OF SIGNIFICANCE: Reproducing the collagen content and stiffness of cancer tissue is crucial in comprehending the properties of cancer and advancing anticancer drug development. Nonetheless, the use of collagen as a scaffold material has posed challenges due to its poor solubility, hindering the replication of a cancer microenvironment. In this study, we have successfully recreated cancer tissue-specific characteristics such as collagen density, stiffness, and the expression of cancer stem cell markers in three-dimensional (3D) colorectal cancer stromal tissue, utilizing a proprietary material known as collagen microfiber (CMF). CMF proves to be an ideal scaffold material for replicating cancer stromal tissue, and these 3D tissues constructed with CMFs hold promise in contributing to our understanding of cancer and the development of therapeutic drugs.Copyright © 2024. Published by Elsevier Ltd.