TY - JOUR
T1 - The role of nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species in the acquisition of metastatic ability of tumor cells
AU - Okada, Futoshi
AU - Kobayashi, Masanobu
AU - Tanaka, Hiroki
AU - Kobayashi, Tokushige
AU - Tazawa, Hiroshi
AU - Iuchi, Yoshihito
AU - Onuma, Kunishige
AU - Hosokawa, Masuo
AU - Dinauer, Mary C.
AU - Hunt, Nicholas H.
N1 - Funding Information:
Supported in part by the Japanese Ministry of Health, Labor, and Welfare (grants-in-aid for cancer research 16-1 and 14-11 to F.O.); and the Japan Society for the Promotion of Science (grants-in-aid 17016007 and 17590334 to F.O.).
PY - 2006/7
Y1 - 2006/7
N2 - We examined the role of phagocyte-derived oxygen radicals in tumor cell acquisition of metastatic phenotype by comparing gp91phox-/- mice and C57BL/6J wild-type (WT) mice. The gp91phox-/- mouse is deficient in the gp91phox gene, an essential subunit of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase that generates superoxide anion. QR-32 fibrosarcoma cells are nonmetastatic but are converted into metastatic tumors once in contact with foreign body (gelatin sponge)-induced phagocytes in vivo. Compared to QR-32 cells co-implanted with the foreign body in WT mice, those in gp91phox-/- mice exhibited reduced metastasis. There was no difference in the incidence of primary tumors after injection of B16BL6 melanoma cells in WT and gp91phox-/- mice. However, after resection of the primary tumors, metastases were reduced in gp91phox-/- mice. Thymosin β4 gene expression and cell motility/invasion were seen in the tumors from WT mice but not in those from gp91phox-/- mice. Adoptive transfer of phagocytes from WT mice, but not those from gp91phox-/- mice, restored the metastatic ability of tumors grown in gp91phox-/- mice. These findings show that tumor metastatic behavior can primarily be endowed by phagocyte-derived superoxide anion and its oxidative metabolites, which are generated through activation of nicotinamide adenine dinucleotide phosphate oxidase.
AB - We examined the role of phagocyte-derived oxygen radicals in tumor cell acquisition of metastatic phenotype by comparing gp91phox-/- mice and C57BL/6J wild-type (WT) mice. The gp91phox-/- mouse is deficient in the gp91phox gene, an essential subunit of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase that generates superoxide anion. QR-32 fibrosarcoma cells are nonmetastatic but are converted into metastatic tumors once in contact with foreign body (gelatin sponge)-induced phagocytes in vivo. Compared to QR-32 cells co-implanted with the foreign body in WT mice, those in gp91phox-/- mice exhibited reduced metastasis. There was no difference in the incidence of primary tumors after injection of B16BL6 melanoma cells in WT and gp91phox-/- mice. However, after resection of the primary tumors, metastases were reduced in gp91phox-/- mice. Thymosin β4 gene expression and cell motility/invasion were seen in the tumors from WT mice but not in those from gp91phox-/- mice. Adoptive transfer of phagocytes from WT mice, but not those from gp91phox-/- mice, restored the metastatic ability of tumors grown in gp91phox-/- mice. These findings show that tumor metastatic behavior can primarily be endowed by phagocyte-derived superoxide anion and its oxidative metabolites, which are generated through activation of nicotinamide adenine dinucleotide phosphate oxidase.
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U2 - 10.2353/ajpath.2006.060073
DO - 10.2353/ajpath.2006.060073
M3 - Article
C2 - 16816381
AN - SCOPUS:33745700697
VL - 169
SP - 294
EP - 302
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 1
ER -