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TISSUE-SPECIFIC STEM CELLS

CD105-Positive Cells in Pulmonary Arterial Blood of Adult Human Lung Cancer Patients Include Mesenchymal Progenitors

^aLaboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan;
^bPathology Division, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, Chiba;
^cGenetics Division, National Cancer Center Research Institute, Tokyo, Japan;
^dThoracic Oncology Division, National Cancer Center Hospital East, Chiba, Japan

Key Words. Mesenchymal progenitor cell • Lung cancer • CD105 • Peripheral blood

Correspondence: 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 on January 14, 2008; accepted for publication on June 25, 2008.

First published online in STEM CELLS EXPRESS  July 31, 2008.

Mesenchymal progenitor cells (MPCs) exhibit fibroblast-like morphology and are multipotent cells capable of differentiating into various mesenchymal tissues. Although MPCs have been found in adult bone marrow and umbilical cord blood, there is still controversy as to whether the MPCs are present in adult human blood. To determine whether they are, we cultured mononuclear cells (MNCs) from the pulmonary arterial blood of lung cancer patients. In 94% (29 of 31) of the cases, fibroblasts were expanded ex vivo and were differentiated into an osteogenic lineage or an adipogenic lineage, depending on the specific inducing medium used. These results indicated that pulmonary arterial blood (PA) in the vicinity of lung cancers contains MPCs (PA-MPCs). The cDNA profiles of PA-MPCs, MPCs derived from bone marrow (BM-MPCs), and lung tissue-derived fibroblasts were clustered with a hierarchical classification algorithm. The expression profiles of PA-MPCs (three cases) and BM-MPCs were clearly separated from those of the tissue-derived fibroblasts, and the profiles of the PA-MPCs from the two patients were separated from those of the BM-MPCs. To identify the source of the PA-MPCs, the MNCs from pulmonary arterial blood were exposed to anti-CD14, anti-CD105, anti-CD3, and anti-CD20 antibodies. CD105⁺ MNCs generated MPCs in eight of eight cases (100%), whereas CD14⁺, CD3⁺, and CD20⁺ mononuclear cells generated MPCs in three of five cases (60%), two of five cases (40%), and zero of three cases (0%), respectively. These findings are the first clear proof that the CD105⁺ MNC fraction in the pulmonary arterial blood of adult lung cancer patients includes MPCs.

Disclosure of potential conflicts of interest is found at the end of this article.