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TISSUE-SPECIFIC STEM CELLS |
aPathology Division, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, Chiba, Japan;
bLaboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan;
cGenetics Division, National Cancer Center Research Institute, Tokyo, Japan;
dThoracic Oncology Divisions, National Cancer Center Hospital East, Chiba, Japan
Key Words. Cancer stromal fibroblast • Lung cancer • Fibroblast progenitor cell
Correspondence: Atsushi Ochiai, M.D., Ph.D., Pathology Division, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, 6-5-1 Kashiwanoha, Kashiwa-City, Chiba 277-8577, Japan. Telephone: 81-4-7134-6855; Fax: 81-4-7134-6865; e-mail: aochiai{at}east.ncc.go.jp
Received July 20, 2006;
accepted for publication March 12, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS March 22, 2007.
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 mm2; 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.
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