Human Barrett's Adenocarcinoma of the Esophagus, Associated Myofibroblasts, and Endothelium Can Arise from Bone Marrow-Derived Cells After Allogeneic Stem Cell Transplant
Human Barrett's Adenocarcinoma of the Esophagus, Associated Myofibroblasts, and Endothelium Can Arise from Bone Marrow-Derived Cells After Allogeneic Stem Cell Transplant
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DOI：
10.1089/scd.2010.0139
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Houghton, JeanMarie
中科院分区：
文献类型：
--
作者：
Hutchinson, Lloyd;Stenstrom, Bjorn;Houghton, JeanMarie
本研究采用小鼠手术模型和人体标本，研究骨髓源性细胞（BMDCs）对食管Barrett腺癌的作用。将表达β-半乳糖苷酶的骨髓移植到野生型小鼠中，然后进行外科食管空肠吻合术，允许将BMDC追踪到外科吻合术中并导致巴雷特化生。一位男性患者接受了女性骨髓移植，后来发展为食管腺癌，他的人体组织使我们能够将供体来源的细胞引导到肿瘤中。使用针对β-半乳糖苷酶（动物研究）和X/Y荧光原位杂交（FISH）（人类研究）的抗体组合，结合针对上皮细胞，成纤维细胞，内皮细胞和白细胞标志物的特异性谱系染色，我们发现骨髓细胞有助于食管腺癌的上皮和基质成分。这些发现表明，BMDC可以产生癌症相关的成纤维细胞，以及直接有助于食管癌的上皮细胞。
This study characterizes the contribution of bone marrow-derived cells (BMDCs) to Barrett's adenocarcinoma of the esophagus using a mouse surgical model of disease and human specimens. Transplantation of bone marrow expressing beta galactosidase into a wild-type mouse, followed by surgical esophagojejunostomy, allowed tracking of BMDCs into the surgical anastomosis and resulting Barrett's metaplasia. Human tissue from a male patient who had been transplanted with female bone marrow and later developed esophageal adenocarcinoma allowed us to tract donor-derived cells into the tumor. Using a combination of antibodies directed against beta-galactosidase (animal studies) and X/Y fluorescent in situ hybridization (FISH) (human studies), combined with specific lineage staining directed against epithelial, fibroblast, endothelial, and leukocyte markers, we show that bone marrow cells contribute to both the epithelial and stromal component of esophageal adenocarcinoma. These findings demonstrate that BMDCs can generate cancer-associated fibroblasts as well as contribute directly to epithelial cells in cancer of the esophagus.