TY - JOUR
T1 - Surgical stress promotes tumor growth in ovarian carcinoma
AU - Lee, Jeong Won
AU - Shahzad, Mian M.K.
AU - Lin, Yvonne G.
AU - Armaiz-Pena, Guillermo
AU - Mangala, Lingegowda S.
AU - Han, Hee Dong
AU - Kim, Hye Sun
AU - Nam, Eun Ji
AU - Jennings, Nicholas B.
AU - Halder, Jyotsnabaran
AU - Nick, Alpa M.
AU - Stone, Rebecca L.
AU - Lu, Chunhua
AU - Lutgendorf, Susan K.
AU - Cole, Steve W.
AU - Lokshin, Anna E.
AU - Sood, Anil K.
PY - 2009/4/15
Y1 - 2009/4/15
N2 - Purpose: Surgical stress has been suggested to facilitate the growth of preexisting micrometastases as well as small residual tumor postoperatively. The purpose of this study was to examine the effects of surgical stress on ovarian cancer growth and to determine underlying mechanisms responsible for increased growth. Experimental Design: To mimic the effects of surgery, we did a laparotomy or mastectomy under isoflurane inhalation on athymic nude mice 4 days after i.p. tumor cell injection. Propranolol infusion via Alzet pumps was used to block the influence of sympathetic nervous system activation by surgical stress. Results: In both HeyA8 and SKOV3ip1 models, the mice in the laparotomy and mastectomy groups had significantly greater tumor weight (P < 0.05) and nodules (P < 0.05) compared with anesthesia only controls. There was no increase in tumor weight following surgery in the β-adrenergic receptor-negative RMG-II model. Propranolol completely blocked the effects of surgical stress on tumor growth, indicating a critical role for β- adrenergic receptor signaling in mediating the effects of surgical stress on tumor growth. In the HeyA8 and SKOV3ip1 models, surgery significantly increased microvessel density (CD31) and vascular endothelial growth factor expression, which were blocked by propranolol treatment. Conclusion: These results indicate that surgical stress could enhance tumor growth and angiogenesis, and β-blockade might be effective in preventing such effects.
AB - Purpose: Surgical stress has been suggested to facilitate the growth of preexisting micrometastases as well as small residual tumor postoperatively. The purpose of this study was to examine the effects of surgical stress on ovarian cancer growth and to determine underlying mechanisms responsible for increased growth. Experimental Design: To mimic the effects of surgery, we did a laparotomy or mastectomy under isoflurane inhalation on athymic nude mice 4 days after i.p. tumor cell injection. Propranolol infusion via Alzet pumps was used to block the influence of sympathetic nervous system activation by surgical stress. Results: In both HeyA8 and SKOV3ip1 models, the mice in the laparotomy and mastectomy groups had significantly greater tumor weight (P < 0.05) and nodules (P < 0.05) compared with anesthesia only controls. There was no increase in tumor weight following surgery in the β-adrenergic receptor-negative RMG-II model. Propranolol completely blocked the effects of surgical stress on tumor growth, indicating a critical role for β- adrenergic receptor signaling in mediating the effects of surgical stress on tumor growth. In the HeyA8 and SKOV3ip1 models, surgery significantly increased microvessel density (CD31) and vascular endothelial growth factor expression, which were blocked by propranolol treatment. Conclusion: These results indicate that surgical stress could enhance tumor growth and angiogenesis, and β-blockade might be effective in preventing such effects.
UR - http://www.scopus.com/inward/record.url?scp=65249085625&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249085625&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-2966
DO - 10.1158/1078-0432.CCR-08-2966
M3 - Article
C2 - 19351748
AN - SCOPUS:65249085625
SN - 1078-0432
VL - 15
SP - 2695
EP - 2702
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -