TY - JOUR
T1 - Operative injury accelerates tumor growth by inducing mobilization and recruitment of bone marrow-derived stem cells
AU - Takemoto, Yoshihiro
AU - Li, Tao Sheng
AU - Kubo, Masayuki
AU - Ohshima, Mako
AU - Ueda, Kazuhiro
AU - Harada, Eijirou
AU - Enoki, Tadahiko
AU - Okamoto, Mariko
AU - Mizukami, Yoichi
AU - Murata, Tomoaki
AU - Hamano, Kimikazu
N1 - Funding Information:
Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan .
PY - 2011/6
Y1 - 2011/6
N2 - Background: Although operative injury is thought generally to worsen the prognosis of cancer patients, the relevant mechanisms are not yet understood fully. We tested the hypothesis that operative injury induces mobilization and recruitment of bone marrow stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Methods: Mice were subjected to an open gastrotomy, and naïve mice were used as controls. The mobilization of bone marrow stem cells was monitored after operation. Using an established tumor model in green fluorescent protein (GFP)+ bone marrow-transplanted chimera mice, we investigated further whether the mobilized stem cells affected tumor growth. Results: Compared with the control, gastrotomy increased the populations of CD34+ cells (6.9 ± 4.5 % vs 3.3 ± 0.4%, P < .05) and CD34+/Flk-1+ cells (0.08 ± 0.02% vs 0.05 ± 0.01%, P < .05) in peripheral blood 12 h after operation. Twelve days after operation, the tumor volume almost doubled in mice after gastrotomy compared with control (580 ± 106 mm3 vs 299 ± 162 mm 3, P < .05). A histologic analysis of tumor tissue revealed that the microvessel density and number of proliferating cells were significantly greater, but those of apoptotic cells were significantly less, in mice after gastrotomy as compared with control. Furthermore, the number of GFP+ cells found in tumor tissue was significantly greater in mice that underwent gastrotomy than in controls. Some of the stained GFP+ cells were positive for CD34 and had been incorporated into microvessels. Administration of AMD3100, which is an antagonist of stromal-cell-derived factor (SDF)-1/CXCR4 signaling pathway, inhibited the recruitment of GFP+ cells and negated completely the acceleration in tumor growth after operation (345 ± 172 mm3, P < .05). Conclusion: Operative injury may induce the mobilization and recruitment of bone marrow stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Inhibition of the SDF-1/CXCR4 signals may represent a new therapeutic strategy for preventing acceleration of tumor growth after operation.
AB - Background: Although operative injury is thought generally to worsen the prognosis of cancer patients, the relevant mechanisms are not yet understood fully. We tested the hypothesis that operative injury induces mobilization and recruitment of bone marrow stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Methods: Mice were subjected to an open gastrotomy, and naïve mice were used as controls. The mobilization of bone marrow stem cells was monitored after operation. Using an established tumor model in green fluorescent protein (GFP)+ bone marrow-transplanted chimera mice, we investigated further whether the mobilized stem cells affected tumor growth. Results: Compared with the control, gastrotomy increased the populations of CD34+ cells (6.9 ± 4.5 % vs 3.3 ± 0.4%, P < .05) and CD34+/Flk-1+ cells (0.08 ± 0.02% vs 0.05 ± 0.01%, P < .05) in peripheral blood 12 h after operation. Twelve days after operation, the tumor volume almost doubled in mice after gastrotomy compared with control (580 ± 106 mm3 vs 299 ± 162 mm 3, P < .05). A histologic analysis of tumor tissue revealed that the microvessel density and number of proliferating cells were significantly greater, but those of apoptotic cells were significantly less, in mice after gastrotomy as compared with control. Furthermore, the number of GFP+ cells found in tumor tissue was significantly greater in mice that underwent gastrotomy than in controls. Some of the stained GFP+ cells were positive for CD34 and had been incorporated into microvessels. Administration of AMD3100, which is an antagonist of stromal-cell-derived factor (SDF)-1/CXCR4 signaling pathway, inhibited the recruitment of GFP+ cells and negated completely the acceleration in tumor growth after operation (345 ± 172 mm3, P < .05). Conclusion: Operative injury may induce the mobilization and recruitment of bone marrow stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Inhibition of the SDF-1/CXCR4 signals may represent a new therapeutic strategy for preventing acceleration of tumor growth after operation.
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U2 - 10.1016/j.surg.2011.02.005
DO - 10.1016/j.surg.2011.02.005
M3 - Article
C2 - 21507448
AN - SCOPUS:79957709003
SN - 0039-6060
VL - 149
SP - 792
EP - 800
JO - Surgery
JF - Surgery
IS - 6
ER -
