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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2757-2763. Prepublished online as a Blood First Edition Paper on November 30, 2004; DOI 10.1182/blood-2004-08-3317. This Article Full Text (PDF) All Versions of this Article: 2004-08-3317v1 105/7/2757    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Okamoto, R. Articles by Takakura, N. Search for Related Content PubMed PubMed Citation Articles by Okamoto, R. Articles by Takakura, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2004 Accepted November 24, 2004 Hematopoietic cells Regulate the angiogenic switch during tumorigenesis Rika Okamoto, Masaya Ueno, Yoshihiro Yamada, Naoko Takahashi, Hideto Sano, Toshio Suda, and Nobuyuki Takakura* Department of Stem Cell Biology, Cancer Research Institute of Kanazawa University, Kanazawa, Japan Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, Tokyo, Japan * Corresponding author; email: ntakaku{at}kenroku.kanazawa-u.ac.jp. Hematopoietic cells (HCs) promote blood vessel formation by producing various pro-angiogenic cytokines and chemokines, and matrix metalloproteinases. We injected mouse colon26 colon cancer cells or human PC3 prostate adenocarcinoma cells into mice and studied the localization of HCs during tumor development. HCs were distributed in the inner tumor mass in all of the tumor tissues examined; however, the localization of HCs in the tumor tissue differed depending on the tumor cell type. In the case of colon 26 tumors, as the tumor grew, many mature HCs migrated into the tumor mass before fine capillary formation was observed. On the other hand, although very few HCs migrated into PC3 tumor tissue, c-Kit-positive hematopoietic stem/progenitor cells accumulated around the edge of the tumor. Bone marrow suppression induced by injection of anti-c-Kit neutralizing antibody, suppressed tumor angiogenesis by different mechanisms according to the tumor cell type: bone marrow suppression inhibited the initiation of sprouting angiogenesis in colon26 tumors, while it suppressed an increase in the caliber of newly developed blood vessels at the tumor edge in PC3 tumors. Our findings suggest that HCs are involved in tumor angiogenesis and regulate the angiogenic switch during tumorigenesis. 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