School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, People's Republic of China.
Harbin Medical University, Harbin 150080, People's Republic of China.
ACS Appl Bio Mater. 2021 Jan 18;4(1):441-450. doi: 10.1021/acsabm.0c00927. Epub 2020 Dec 15.
Cancer stem cells (CSCs) are self-renewing and constitute the primary cause of cancer relapse post-cancer therapy. The CSC niche is composed of various nonmalignant stromal cells that support CSCs' survival during cancer chemoradiotherapy. Understanding the cross-talk between CSCs and stromal cells could pave the way for developing therapeutic strategies to eradicate CSCs. Traditionally, CSC research has been relying on animal models, which can give rise to complications and poor translation in clinical practice. An efficient model to co-culture CSCs and stromal cells is urgently needed. Hence, we leveraged our expertise in enriching CSCs from in vitro cell lines with a 3D alginate-based platform, as reported previously. We established a 3D co-culture system that allowed us to study the interactions between stromal cells and CSCs over an extended period. We showed that the self-renewal capacity and stemness of CSCs were significantly enhanced when co-cultured with 3D cultured human umbilical vein endothelial cells (HUVECs) or a human monocyte cell line (THP1). Strikingly, the expression of MDR1 in 3D co-cultured CSCs was upregulated, leading to enhanced chemotoxic drug tolerance. We suggest that our in vitro co-culture model can impact CSC research and clinical practice when the goal is to develop therapeutics that target and eradicate CSCs by targeting stromal cells.
癌症干细胞 (CSCs) 具有自我更新能力，是癌症治疗后复发的主要原因。CSC 生态位由各种非恶性基质细胞组成，这些细胞在癌症放化疗期间支持 CSCs 的存活。了解 CSCs 与基质细胞之间的相互作用可能为开发消除 CSCs 的治疗策略铺平道路。传统上，CSC 研究依赖于动物模型，这可能会在临床实践中引起并发症和转化不良。因此，我们迫切需要一种有效的共培养 CSCs 和基质细胞的模型。为此，我们利用先前报道的从体外细胞系中富集 CSCs 的 3D 藻酸盐平台方面的专业知识，建立了一个 3D 共培养系统，使我们能够在较长时间内研究基质细胞和 CSCs 之间的相互作用。结果表明，与 3D 培养的人脐静脉内皮细胞 (HUVECs) 或人单核细胞系 (THP1) 共培养后，CSCs 的自我更新能力和干细胞特性显著增强。令人惊讶的是，3D 共培养 CSCs 中 MDR1 的表达上调，导致对化疗药物的耐受性增强。我们建议，当目标是开发针对基质细胞并通过靶向基质细胞来消除 CSCs 的治疗方法时，我们的体外共培养模型可以影响 CSC 研究和临床实践。
