癌症相关基质细胞促进MMP2阳性骨髓来源细胞对口腔鳞状细胞癌侵袭的作用。
Cancer-Associated Stromal Cells Promote the Contribution of MMP2-Positive Bone Marrow-Derived Cells to Oral Squamous Cell Carcinoma Invasion.
作者信息
Oo May Wathone, Kawai Hotaka, Takabatake Kiyofumi, Shan Qiusheng, Eain Htoo Shwe, Sukegawa Shintaro, Nakano Keisuke, Nagatsuka Hitoshi
机构信息
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan.
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan.
出版信息
Cancers (Basel). 2021 Dec 28;14(1):137. doi: 10.3390/cancers14010137.
Tumor stromal components contribute to tumor development and invasion. However, the role of stromal cells in the contribution of bone marrow-derived cells (BMDCs) in oral squamous cell carcinoma (OSCC) invasion is unclear. In the present study, we created two different invasive OSCC patient-derived stroma xenografts (PDSXs) and analyzed and compared the effects of stromal cells on the relation of BMDCs and tumor invasion. We isolated stromal cells from two OSCC patients: less invasive verrucous OSCC (VSCC) and highly invasive conventional OSCC (SCC) and co-xenografted with the OSCC cell line (HSC-2) on green fluorescent protein (GFP)-positive bone marrow (BM) cells transplanted mice. We traced the GFP-positive BM cells by immunohistochemistry (IHC) and detected matrix metalloproteinase 2 (MMP2) expression on BM cells by double fluorescent IHC. The results indicated that the SCC-PDSX promotes MMP2-positive BMDCs recruitment to the invasive front line of the tumor. Furthermore, microarray analysis revealed that the expressions of interleukin 6; mRNA and interleukin 1 beta; mRNA were higher in SCC stromal cells than in VSCC stromal cells. Thus, our study first reports that IL-6 and IL1B might be the potential stromal factors promoting the contribution of MMP2-positive BMDCs to OSCC invasion.
肿瘤基质成分有助于肿瘤的发展和侵袭。然而，基质细胞在骨髓来源细胞（BMDCs）促进口腔鳞状细胞癌（OSCC）侵袭中的作用尚不清楚。在本研究中，我们创建了两种不同侵袭性的OSCC患者来源的基质异种移植模型（PDSXs），并分析和比较了基质细胞对BMDCs与肿瘤侵袭关系的影响。我们从两名OSCC患者中分离出基质细胞：侵袭性较低的疣状OSCC（VSCC）和侵袭性较高的传统OSCC（SCC），并将其与OSCC细胞系（HSC-2）共同异种移植到移植了绿色荧光蛋白（GFP）阳性骨髓（BM）细胞的小鼠体内。我们通过免疫组织化学（IHC）追踪GFP阳性的BM细胞，并通过双重荧光IHC检测BM细胞上基质金属蛋白酶2（MMP2）的表达。结果表明，SCC-PDSX促进MMP2阳性BMDCs募集到肿瘤的侵袭前沿。此外，微阵列分析显示，白细胞介素6；mRNA和白细胞介素1β；mRNA在SCC基质细胞中的表达高于VSCC基质细胞。因此，我们的研究首次报道IL-6和IL1B可能是促进MMP2阳性BMDCs对OSCC侵袭作用的潜在基质因子。
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