Abstract:
The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. The macrophages are considered as the most abundant immune cells in tumor microenvironment and their function in tumorigenesis is interesting. Macrophages can be present as M1 and M2 polarization that show anti-cancer and oncogenic activities, respectively. Tumor-associated macrophages (TAMs) mainly have M2 polarization and they increase tumorigenesis due to secretion of factors, cytokines and affecting molecular pathways. Hepatocellular carcinoma (HCC) is among predominant tumors of liver that in spite of understanding its pathogenesis, the role of tumor microenvironment in its progression still requires more attention. The presence of TAMs in HCC causes an increase in growth and invasion of HCC cells and one of the reasons is induction of glycolysis that such metabolic reprogramming makes HCC distinct from normal cells and promotes its malignancy. Since M2 polarization of TAMs stimulates tumorigenesis in HCC, molecular networks regulating M2 to M1 conversion have been highlighted and moreover, drugs and compounds with the ability of targeting TAMs and suppressing their M2 phenotypes or at least their tumorigenesis activity have been utilized. TAMs increase aggressive behavior and biological functions of HCC cells that can result in development of therapy resistance. Macrophages can provide cell-cell communication in HCC by secreting exosomes having various types of biomolecules that transfer among cells and change their activity. Finally, non-coding RNA transcripts can mainly affect polarization of TAMs in HCC.
摘要:
肿瘤微环境是一个由正常、癌症和免疫细胞。巨噬细胞被认为是肿瘤微环境中最丰富的免疫细胞,其在肿瘤发生中的功能令人感兴趣。巨噬细胞可以以M1和M2极化的形式存在,显示出抗癌和致癌活性,分别。肿瘤相关巨噬细胞(TAMs)主要具有M2极化,它们由于分泌因子而增加肿瘤发生,细胞因子和影响分子途径。肝细胞癌(HCC)是肝脏的主要肿瘤,尽管了解其发病机理,肿瘤微环境在其进展中的作用仍需引起更多关注。TAM在HCC中的存在导致HCC细胞的生长和侵袭增加,并且其中一个原因是糖酵解的诱导,使得这种代谢重编程使得HCC不同于正常细胞并促进其恶性化。由于TAM的M2极化刺激HCC的肿瘤发生,调节M2到M1转化的分子网络得到了强调,此外,已经利用了具有靶向TAM和抑制其M2表型或至少其肿瘤发生活性的能力的药物和化合物。TAM会增加HCC细胞的攻击行为和生物学功能,从而导致治疗耐药性的发展。巨噬细胞可以通过分泌具有在细胞之间转移并改变其活性的各种类型的生物分子的外泌体来提供HCC中的细胞-细胞通讯。最后,非编码RNA转录本主要影响肝癌中TAMs的极化。