Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Biomater Sci. 2019 May 28;7(6):2264-2271. doi: 10.1039/c9bm00155g.
Hyaluronic acid (HA) is found in various tumor tissues, and is considered tumor-associated extracellular matrix (ECM). Within this tumor-associated ECM, stromal cells, especially immune cells, are involved in tumor progression. However, the effects of tumor-associated ECM on the characteristics of immune cells remain unexplored. Therefore, we studied the triggering effect of HA on spontaneous M2-like polarity of monocytes/macrophages using HA-mixed collagen (HA-COL) matrix. In the presence of HA, expression of the HA receptor (CD44) and M2 polarity-related genes was upregulated in human monocytes (THP-1 cells). We confirmed the CD44-mediated activation of STAT3 in THP-1 cells cultured in an HA-rich environment. Furthermore, when we induced the THP-1 cells to differentiate into cells with M1 or M2 polarity within an HA-rich environment, the HA-rich environment influenced the direction of induction. Our findings might improve understanding of the crosstalk between immune cells and tumor-associated ECM, and facilitate development of tumor immunotherapy strategies.
透明质酸（HA）存在于各种肿瘤组织中，被认为是肿瘤相关细胞外基质（ECM）的一部分。在这种肿瘤相关 ECM 中，基质细胞，特别是免疫细胞，参与肿瘤的进展。然而，肿瘤相关 ECM 对免疫细胞特征的影响仍有待探索。因此，我们使用 HA 混合胶原（HA-COL）基质研究了 HA 对单核细胞/巨噬细胞自发 M2 样极性的触发作用。在 HA 存在的情况下，人单核细胞（THP-1 细胞）中 HA 受体（CD44）和 M2 极性相关基因的表达上调。我们证实了在富含 HA 的环境中培养的 THP-1 细胞中 CD44 介导的 STAT3 激活。此外，当我们在富含 HA 的环境中诱导 THP-1 细胞分化为具有 M1 或 M2 极性的细胞时，富含 HA 的环境会影响诱导的方向。我们的研究结果可能有助于加深对免疫细胞与肿瘤相关 ECM 之间相互作用的理解，并促进肿瘤免疫治疗策略的发展。
