Presence of human circulating progenitor cells for cancer stromal fibroblasts in the blood of lung cancer patients
Presence of human circulating progenitor cells for cancer stromal fibroblasts in the blood of lung cancer patients
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DOI：
10.1634/stemcells.2006-0449
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发表时间：
2007-06-01
期刊：
影响因子：
5.2
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Ishii, Genicriro;Ito, Ta-Kashi;Ochiai, Atsushi
最近的动物数据表明，癌症诱导的间质包括血液来源的成纤维细胞和组织来源的成纤维细胞。在这项研究中，从肺癌患者的肺静脉血中分离出单个核细胞进行培养，以证实血源性成纤维细胞的存在。在34%(16/47)的病例中，成纤维细胞形态的梭形细胞以杂乱排列的方式增殖，波形蛋白和I型胶原阳性，而特异性肌源性和内皮标志物阴性。用层次分类算法对血源性成纤维细胞、组织源性(肺)成纤维细胞、人血管平滑肌细胞(HSMCs)和脐静脉内皮细胞(HUVECs)的基因表达谱进行了聚类分析。血源性成纤维细胞的特征明显地与组织来源的成纤维细胞、HSMCs和HUVECs分离。将肺癌患者血液中标记CFSE的人单核细胞移植到非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠体内，发现癌巢周围可见CFSE标记的成纤维细胞。我们调查了血源性成纤维细胞阳性患者的几个临床病理因素。血源性成纤维细胞阳性患者的原发性肺癌中心纤维面积显著大于阴性患者(123+/-29对59+/-13 mm(2)；p=0.02)。我们的结果表明，人肺癌周围的血液中含有成纤维细胞前体细胞，这些细胞具有向肿瘤间质迁移并分化为具有不同于组织源性成纤维细胞的生物学特性的能力。
Recent animal data have suggested that cancer-induced stroma consists of blood-borne fibroblasts as well as tissue-derived fibroblasts. In this study, mononuclear cells isolated from the pulmonary vein blood of lungs resected from lung cancer patients were cultured to confirm the presence of blood-borne fibroblast. In 34% (16 of 47) of the cases, spindle cells with fibroblast morphology proliferated in a disarrayed fashion and were positive for vimentin and collagen type I but negative for both specific myogenic and endothelial markers. The cDNA profiles of blood-borne fibroblasts, tissue-derived (lung) fibroblasts, human vascular smooth muscle cells (HSMCs), and umbilical vein endothelial cells (HUVECs) were clustered with a hierarchical classification algorithm. The profiles of the blood-borne fibroblasts were clearly isolated from those of the tissue-derived fibroblasts, HSMCs, and HUVECs. When carboxyfluorescein succinyl ester (CFSE)-labeled human mononuclear cells from the blood of lung cancer patients were transferred into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice engrafted with a human lung cancer xenograft, CFSE-labeled fibroblasts were found around the cancer nests. We investigated the several clinicopathological factors of blood-borne fibroblast- positive patients. The blood-borne fibroblast-positive cases had a significantly larger central fibrotic area in primary lung cancer than in the negative cases (123 +/- 29 vs. 59 +/- 13 mm(2); p =.02). Our results indicated that the blood in the vicinity of human lung cancer contains fibroblast progenitor cells that have the capacity to migrate into the cancer stroma and differentiate into fibroblasts having biological characteristics different from those of tissue-derived fibroblasts.