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Tissue-Specific Stem Cells |
1 Pathology Division, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, Chiba, Japan
2 Pathology Division, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, Chiba, Japan; Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan
3 Genetics Division, National Cancer Center Research Institute, Tokyo, Japan
4 Thoracic Oncology Divisions, National Cancer Center Hospital East, Chiba, Japan
* To whom correspondence should be addressed. E-mail: aochiai{at}east.ncc.go.jp.
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Abstract |
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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 disarray fashion and were positive for vimentin, 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 non-obese 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±29mm2 vs 59±13mm2. P=0.02). Our results indicated that the blood in the icinity 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.
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