Surgical stress promotes tumor growth in ovarian carcinoma.
Title | Surgical stress promotes tumor growth in ovarian carcinoma. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Lee J-W, Shahzad MMK, Lin YG, Armaiz-Pena G, Mangala LS, Han H-D, Kim H-S, Nam EJi, Jennings NB, Halder J, Nick AM, Stone RL, Lu C, Lutgendorf SK, Cole SW, Lokshin AE, Sood AK |
Journal | Clin Cancer Res |
Volume | 15 |
Issue | 8 |
Pagination | 2695-702 |
Date Published | 2009 Apr 15 |
ISSN | 1078-0432 |
Keywords | Adrenergic beta-Antagonists, Animals, Antigens, CD31, Carcinoma, Cell Line, Tumor, Cell Proliferation, Cytokines, Female, Humans, Mice, Mice, Nude, Microvessels, Neovascularization, Pathologic, Ovarian Neoplasms, Proliferating Cell Nuclear Antigen, Propranolol, Receptors, Adrenergic, beta, Stress, Psychological, Transplantation, Heterologous, Vascular Endothelial Growth Factor A |
Abstract | 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 beta-adrenergic receptor-negative RMG-II model. Propranolol completely blocked the effects of surgical stress on tumor growth, indicating a critical role for beta-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 beta-blockade might be effective in preventing such effects. |
DOI | 10.1158/1078-0432.CCR-08-2966 |
Alternate Journal | Clin. Cancer Res. |
PubMed ID | 19351748 |
PubMed Central ID | PMC2746852 |
Grant List | CA109298 / CA / NCI NIH HHS / United States CA110793 / CA / NCI NIH HHS / United States P50 CA083639 / CA / NCI NIH HHS / United States R01 CA109298 / CA / NCI NIH HHS / United States R01 CA109298-05 / CA / NCI NIH HHS / United States R01 CA110793 / CA / NCI NIH HHS / United States R01 CA110793-05 / CA / NCI NIH HHS / United States R01 CA116778 / CA / NCI NIH HHS / United States R01 CA116778-03 / CA / NCI NIH HHS / United States T32 CA101642 / CA / NCI NIH HHS / United States |