Pro-inflammatory type-1 and anti-inflammatory type-2 macrophages differentially modulate cell survival and invasion of human bladder carcinoma T24 cells
Pro-inflammatory type-1 and anti-inflammatory type-2 macrophages differentially modulate cell survival and invasion of human bladder carcinoma T24 cells
复制标题
DOI：
10.1016/j.molimm.2011.04.022
复制
发表时间：
2011-07-01
影响因子：
3.6
通讯作者：
Reyes-Moreno, Carlos
中科院分区：
文献类型：
--
作者：
Dufresne, Mathieu;Dumas, Genevieve;Reyes-Moreno, Carlos
许多研究结果表明，炎症可能在膀胱癌发生和癌症疾病进展中起重要作用。虽然巨噬细胞（M phi s）构成人膀胱癌基质的主要炎性组分，但这种炎性白细胞在肿瘤细胞存活和侵袭中的调节作用仍然是难以捉摸的。采用人膀胱癌T24细胞和单核细胞源性巨噬细胞研究促炎性1型（M phi-1）和抗炎性2型（M phi-2）巨噬细胞在调节膀胱癌细胞行为中的相对作用。细胞间研究表明，与单独培养T24细胞相比，T24细胞/M phi-2共培养物中的活细胞数相当高，但T24细胞/M phi-1共培养物中的活细胞数较低。M phi-1衍生因子抑制T24细胞生长，但不能诱导caspase-3介导的凋亡。M phi-2衍生因子具有抑制M phi-1衍生因子对T24细胞生长的抑制作用的能力。外源性白细胞介素（IL）-10逆转T24细胞/M phi-1细胞共培养物中M phi-1介导的生长停滞。进一步的分析表明M phi-1衍生因子诱导T24细胞肿瘤坏死因子（TNF）-α基因表达，促进细胞侵袭，并增加磷酸肌醇3-激酶（PI 3-K）/Akt信号通路活性。抑制T24细胞中PI 3-K活化或阻断T24细胞/M phi-1细胞共培养物中TNF α受体可降低细胞侵袭力，但不影响T24细胞活力。基于这些观察结果，我们提出UBC细胞和浸润性巨噬细胞之间类似的功能相互作用可以在体内发生，并在膀胱癌进展过程中影响肿瘤细胞的存活和侵袭。皇冠版权所有（C）2011由爱思唯尔有限公司出版。保留所有权利。
Findings from numerous studies suggest that inflammation is likely to have an important role in bladder carcinogenesis and cancer disease progression. While macrophages (M phi s) constitute a major inflammatory component of the stroma of human bladder carcinoma, the regulatory role of such inflammatory leukocytes in tumor cell survival and invasion remains elusive. Human urothelial bladder cancer (UBC) T24 cells and monocyte-derived macrophages were used to study the relative contribution of proinflammatory type-1 (M phi-1) and anti-inflammatory type-2 (M phi-2) macrophages in the regulation of UBC cell behaviour. Cell-to-cell studies indicated that the number of viable cells were considerable higher in T24 cell/M phi-2 cocultures but lower in T24 cell/M phi-1 cocultures when compared to cultures of T24 cells alone. M phi-1-derived factors inhibit T24 cell growth but fail to induce caspase-3-mediated apoptosis. M phi-2-derived factors have the ability to suppress the inhibitory effect of M phi-1-derived factors on T24 cell growth. Exogenous interleukin (IL)-10 reverse M phi-1-mediated arrest growth in T24 cell/M phi-1 cell cocultures. Further analyses showed that M phi-1-derived factors induced tumor necrosis factor (TNF)-alpha gene expression, promoted cellular invasiveness and increased phosphoinositide 3-kinase (PI 3-K)/Akt signaling pathway activity in T24 cells. Inhibition of PI 3-K activation in T24 cells or blockade of TNF alpha receptor in T24 cell/M phi-1 cell cocultures decreased cellular invasiveness but did not affect T24 cell viability. Based on these observations, we propose that similar functional interactions between UBC cells and infiltrating macrophages can take place in vivo and influence tumor cell survival and invasion during bladder cancer progression. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.