Hematopoietic cells regulate the angiogenic switch during tumorigenesis.
Hematopoietic cells (HCs) promote blood vessel formation by producing various proangiogenic 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 colon26 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+ 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.
Okamoto
Rika
R
Department of Stem Cell Biology, Cancer Research Institute of Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Ueno
Masaya
M
Yamada
Yoshihiro
Y
Takahashi
Naoko
N
Sano
Hideto
H
Suda
Toshio
T
Takakura
Nobuyuki
N
D000230:Adenocarcinoma / Q000098:blood supply / Q000503:physiopathology*; D000818:Animals; D000906:Antibodies; D001808:Blood Vessels / Q000502:physiology; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000502:physiology; D003110:Colonic Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007970:Leukopenia / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism
D000906:Antibodies; D019009:Proto-Oncogene Proteins c-kit; D042787:Receptor, TIE-2