Yang Zhigang, Yao Hong, Fei Fei, Li Yuwei, Qu Jie, Li Chunyuan, Zhang Shiwu
Departments of Pathology, Baodi Traditional Chinese Medicine Hospital, Baodi District, Tianjin, 300121, People's Republic of China.
Department of thoracic Surgery, Tianjin Union Medical Center, Tianjin, 300121, People's Republic of China.
J Cancer Res Clin Oncol. 2018 Apr;144(4):617-627. doi: 10.1007/s00432-018-2598-4. Epub 2018 Feb 7.
During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels.
In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia.
An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.
在发育和肿瘤进展过程中，细胞需要充足的血液供应来维持发育和快速生长。据报道，肿瘤生长存在三种血液供应模式：内皮依赖性血管、镶嵌血管和血管生成拟态（VM）。VM最早在具有高度侵袭性的葡萄膜黑色素瘤中被报道，肿瘤细胞模拟形成VM血管壁的内皮细胞的存在和功能。镶嵌血管壁随机排列着内皮细胞和肿瘤细胞。我们之前提出了一个三阶段过程，始于VM，发展为镶嵌血管，最终导致内皮依赖性血管。然而，VM通道形成所特有的许多现象仍有待阐明，例如在VM血管与内皮依赖性血管连接之前红细胞的来源。
在成年人中，普遍认为红细胞是由骨髓中的造血干细胞产生的。相比之下，胚胎组织通过形成血岛来获取氧气，在没有成熟红细胞的情况下，血岛主要由与氧气具有更高亲和力的胚胎血红蛋白组成。我们实验室最近的数据表明，胚胎造血机制也存在于癌组织中，特别是当这些组织处于缺氧等环境应激状态时。我们回顾了来自体外和体内诱导多能干细胞的证据，以支持这种在正常细胞和癌细胞中先前未被充分认识的细胞功能，包括产生红细胞的能力。我们还将总结目前对肿瘤血管生成、VM以及我们最近关于多倍体巨癌细胞的研究工作，重点是它们在缺氧条件下产生红细胞的能力及其与肿瘤生长的关联。
癌细胞中存在一种替代的胚胎途径来获取氧气，特别是当它们处于缺氧条件下时。
