Differentiation and roles of bone marrow-derived cells on the tumor microenvironment of oral squamous cell carcinoma
Differentiation and roles of bone marrow-derived cells on the tumor microenvironment of oral squamous cell carcinoma
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DOI：
10.3892/ol.2019.11045
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发表时间：
2019-12-01
期刊：
影响因子：
2.9
通讯作者：
Nagatsuka, Hitoshi
中科院分区：
文献类型：
--
作者：
Anqi, Chang;Takabatake, Kiyofumi;Nagatsuka, Hitoshi
间质影响肿瘤的性质和动力学。以往的研究表明，骨髓源性细胞（BMDCs）具有向基质细胞分化的能力。然而，BMDCs在口腔鳞状细胞癌中的特性和作用尚不清楚。因此，当前的研究通过追踪移植小鼠模型中绿色荧光蛋白（GFP）标记的BMDC来研究它们的位置和特征。照射后，向BALB-c nu-nu小鼠注射来自C57 BL/6-BALB-C-nu/nu-GFP转基因小鼠的骨髓细胞。然后在这些受体小鼠的头部皮下注射人鳞状细胞癌-2细胞。随后进行GFP、波形蛋白、CD 11b、CD 31和α-平滑肌肌动蛋白（SMA）的免疫组织化学，以及GFP-波形蛋白、GFP-CD 11b、GFP-CD 31和GFP-α-SMA的双荧光免疫组织化学。肿瘤间质中可见大量圆形的GFP阳性细胞，提示BMDCs在肿瘤发生中起主导作用。波形蛋白（+）GFP（+）细胞也可能是源自骨髓的癌症相关基质的成员。本研究中鉴定的圆形或梭形CD 11b（+）GFP（+）细胞可能是来源于骨髓的巨噬细胞。CD 31（+）GFP（+）细胞表现出向骨髓源性成血管细胞的高度倾向。结果还表明，纺锤形的α-SMA（+）GFP（+）细胞不太可能代表骨髓来源的癌症相关成纤维细胞。BMDCs聚集在肿瘤微环境中，表现出多系潜能，参与肿瘤发生、肿瘤侵袭和血管生成等重要过程。
The stroma affects the properties and dynamics of the tumor. Previous studies have demonstrated that bone marrow-derived cells (BMDCs) possess the capability of differentiating into stromal cells. However, the characteristics and roles of BMDCs in oral squamous cell carcinoma remain unclear. The current study therefore investigated their locations and features by tracing green fluorescent protein (GFP)-labeled BMDCs in a transplantation mouse model. After irradiation, BALB-c nu-nu mice were injected with bone marrow cells from C57BL/6-BALB-C-nu/nu-GFP transgenic mice. These recipient mice were then injected subcutaneously in the head with human squamous cell carcinoma-2 cells. Immunohistochemistry for GFP, Vimentin, CD11b, CD31 and alpha-smooth muscle actin (SMA), and double-fluorescent immunohistochemistry for GFP-Vimentin, GFP-CD11b, GFP-CD31 and GFP-alpha-SMA was subsequently performed. Many round-shaped GFP-positive cells were observed in the cancer stroma, which indicated that BMDCs served a predominant role in tumorigenesis. Vimentin(+) GFP(+) cells may also be a member of the cancer-associated stroma, originating from bone marrow. Round or spindle-shaped CD11b(+) GFP(+) cells identified in the present study may be macrophages derived from bone marrow. CD31(+)GFP(+) cells exhibited a high tendency towards bone marrow-derived angioblasts. The results also indicated that spindle-shaped alpha-SMA(+) GFP(+) cells were not likely to represent bone marrow-derived cancer-associated fibroblasts. BMDCs gathering within the tumor microenvironment exhibited multilineage potency and participated in several important processes, such as tumorigenesis, tumor invasion and angiogenesis.