Surgical Stress Promotes Tumor Growth in Ovarian Carcinoma

Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Clinical Cancer Research (Impact Factor: 8.19). 04/2009; 15(8):2695-702. DOI: 10.1158/1078-0432.CCR-08-2966
Source: PubMed

ABSTRACT 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.
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.
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.
These results indicate that surgical stress could enhance tumor growth and angiogenesis, and beta-blockade might be effective in preventing such effects.

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Available from: Guillermo N Armaiz-Pena, Nov 17, 2014
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    • "Surgery is a key cancer therapy and is still the most effective means to treat human solid cancers, which have not yet metastasised (Ceelen et al, 2013). However, tissue damage is implicated as a possible trigger in the development of various cancers (Combemale et al, 2007; Lee et al, 2009; Kasper et al, 2011; Senet et al, 2012) and may provide a favourable niche for tumour reoccurrence (Hofer et al, 1998), as well as facilitating the growth of pre-existing micro-metastases (Bogden et al, 1997), suggesting that surgery may have clinical consequences beyond simply removing the primary cancer (Kuraishy et al, 2011; O&apos;Leary et al, 2013). Classic studies have shown that wounding can lead to tumourigenesis (Hennings & Boutwell, 1970; Clark-Lewis & Murray, 1978; Leder et al, 1990); for example, wounding Rous sarcoma virus-infected chickens led to 100% tumour formation at the injured site (Sieweke et al, 1990), and transgenic mice carrying the v-jun oncogene developed dermal fibrosarcomas after full thickness wounding, whereas identical wounds in non-transgenic mice healed without tumour formation (Schuh et al, 1990). "
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    • "It was reported that propranolol inhibited the promigratory effect of norepinephrine and reduced metastases formation in BALB/c nude mice (Palm et al., 2006). Wound healing and tumor progression both involve similar processes such as cell proliferation, inflammation, and angiogenesis (Lee et al., 2009). One of the important characters related to process of tumor cell penetration is motility. "
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