The administration of multipotent stromal cells at precancerous stage precludes tumor growth and epithelial dedifferentiation of oral squamous cell carcinoma
The administration of multipotent stromal cells at precancerous stage precludes tumor growth and epithelial dedifferentiation of oral squamous cell carcinoma
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DOI：
10.1016/j.scr.2016.11.016
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发表时间：
2017-01-01
影响因子：
1.2
通讯作者：
Conget, Paulette
中科院分区：
文献类型：
--
作者：
Bruna, Flavia;Arango-Rodriguez, Martha;Conget, Paulette
多能基质细胞（MSCs）被认为是一种强大的治疗工具。当它们进入肿瘤，分泌营养和血管生成因子，抑制免疫反应时，它们在癌变中的作用是一个有争议的问题。在世界范围内，口腔鳞状细胞癌（OSCC）是第五大最常见的上皮性癌症。我们的目的是确定在癌前阶段给药MSC是否会改变OSCC的自然进展。在叙利亚仓鼠颊袋内局部应用DMBA诱导OSCC。在乳头状瘤期，局部给予3 × 10(6)个同种异体骨髓来源的间充质干细胞。4周后，对病变进行体积、分层（组织学）、增殖（Ki-67）、凋亡（Caspase 3 cleaved）、脉管系统（ASMA）、炎症（白细胞浸润）、分化（CK1和CK4）和基因表达谱（mRNA）的研究。在接受MSCs的个体中发现的肿瘤比载体组小（87 +/- 80对54 +/- 62 mm， p < 0.05）。MSCs处理后的病变细胞增殖率比未处理的低2倍，细胞凋亡率比未处理的高2.5倍。后者呈现去分化细胞，前者保持分化细胞（细胞角蛋白和基因表达谱与正常组织相似）。因此，在乳头状瘤期给药MSC可阻止OSCC的肿瘤生长和上皮去分化。(C) 2016由Elsevier B.V.发布。这是一篇基于CC by - nc - nd许可的开放获取文章。
Multipotent stromal cells (MSCs) are envisioned as a powerful therapeutic tool. As they home into tumors, secrete trophic and vasculogenic factors, and suppress immune response their role in carcinogenesis is a matter of controversy. Worldwide oral squamous cell carcinoma (OSCC) is the fifth most common epithelial cancer. Our aim was to determine whether MSC administration at precancerous stage modifies the natural progression of OSCC.OSCC was induced in Syrian hamsters by topical application of DMBA in the buccal pouch. At papilloma stage, the vehicle or 3 x 10(6) allogenic bone marrow-derived MSCs were locally administered. Four weeks later, the lesions were studied according to: volume, stratification (histology), proliferation (Ki-67), apoptosis (Caspase 3 cleaved), vasculature (ASMA), inflammation (Leukocyte infiltrate), differentiation (CK1 and CK4) and gene expression profile (mRNA).Tumors found in individuals that received MSCs were smaller than those presented in the vehicle group (87 +/- 80 versus 54 +/- 62 mm(3), p < 0.05). The rate of proliferation was two times lower and the apoptosis was 2.5 times higher in lesions treated with MSCs than in untreated ones. While the laters presented dedifferentiated cells, the former maintained differentiated cells (cytokeratin and gene expression profile similar to normal tissue). Thus, MSC administration at papilloma stage precludes tumor growth and epithelial dedifferentiation of OSCC. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.