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Molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and carbon dioxide pneumoperitoneum: a syngeneic mouse model with controlled respiratory support

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Abstract

Background

The mechanisms promoting postoperative peritoneal tumor dissemination are unclear. This study aimed to investigate postoperative tumor dissemination over time on both tissue and molecular levels.

Methods

For this study, C57BL6 mice were randomized into four groups: anesthesia alone (control), carbon dioxide (CO2) pneumoperitoneum at low (2 mmHg) or high (8 mmHg) intraperitoneal pressure (IPP), and laparotomy. A mouse ovarian cancer cell line (ID8) was injected intraperitoneally just before surgery. The groups were further subdivided into three groups, and a laparotomy was performed to evaluate tumor dissemination on postoperative day (POD) 7, 14, or 42.

Results

The incidence of cancer cell invasion into the muscle layers of the abdominal wall was significantly higher in the laparotomy and high-IPP groups than in the low-IPP and control groups on PODs 7 and 42. Expression levels of beta 1 integrin, cMet, urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), and type-1 plasminogen activator inhibitor (PAI-1) mRNA in the disseminated nodules were not significantly different among the four groups on POD 7. However, the expression levels of all these genes in the disseminated nodules in the laparotomy group were significantly higher on POD 14 than on POD 7. They then returned to control levels on POD 42. There were no significant differences in the expression levels of any of these genes among the groups on POD 42.

Conclusions

The current study suggests that the molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and CO2 pneumoperitoneum. Therefore, strategies targeting postoperative tumor dissemination likely will need to account for the surgical environment.

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References

  1. Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP (2006) Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 243:212–222

    Article  PubMed  Google Scholar 

  2. Lacy AM, García-Valdecasas JC, Delgado S, Castells A, Taurá P, Piqué JM, Visa J (2002) Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 359:2224–2229

    Article  PubMed  Google Scholar 

  3. Leung KL, Kwok SP, Lam SC, Lee JF, Yiu RY, Ng SS, Lai PB, Lau WY (2004) Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial. Lancet 363:1187–1192

    Article  PubMed  Google Scholar 

  4. Tan DS, Agarwal R, Tan DS (2006) Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol 11:925–934

    Article  Google Scholar 

  5. Liotta LA, Kohn EC (2001) The microenvironment of the tumour–host interface. Nature 411:375–379

    Article  PubMed  CAS  Google Scholar 

  6. Freedman RS, Deavers M, Liu J, Wang E (2004) Peritoneal inflammation: a microenvironment for epithelial ovarian cancer (EOC). J Transl Med 2:23

    Article  PubMed  Google Scholar 

  7. Wang E, Ngalame Y, Panelli MC, Nguyen-Jackson H, Deavers M, Mueller P, Hu W, Savary CA, Kobayashi R, Freedman RS, Marincola FM (2005) Peritoneal and subperitoneal stroma may facilitate regional spread of ovarian cancer. Clin Cancer Res 11:113–122

    PubMed  CAS  Google Scholar 

  8. Bourdel N, Matsuzaki S, Bazin JE, Pouly JL, Mage G, Canis M (2007) Peritoneal tissue oxygen tension during a carbon dioxide pneumoperitoneum in a mouse laparoscopic model with controlled respiratory support. Hum Reprod 22:1149–1155

    Article  PubMed  Google Scholar 

  9. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 11:891–899

    Article  Google Scholar 

  10. Crowther M, Brown NJ, Bishop ET, Lewis CE (2001) Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol 70:478–490

    PubMed  CAS  Google Scholar 

  11. Lewis C, Murdoch C (2005) Macrophage responses to hypoxia: implications for tumor progression and anticancer therapies. Am J Pathol 167:627–635

    PubMed  CAS  Google Scholar 

  12. U.S. Department of Health and Human Services, Public Health Service (1985) Guide for the care and use of laboratory animals, revised. National Institute of Health (NIH publication no. 86–23), Bethesda, MD

  13. Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawfik O, Persons DL, Smith PG, Terranova PF (2000) Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogenesis 21:585–591

    Article  PubMed  CAS  Google Scholar 

  14. Bouvy ND, Marquet RL, Jeekel H, Bonjer HJ (1996) Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases. Ann Surg 224:694–700

    Article  PubMed  CAS  Google Scholar 

  15. Canis M, Botchorishvili R, Wattiez A, Mage G, Pouly JL, Bruhat MA (1998) Tumor growth and dissemination after laparotomy and CO2 pneumoperitoneum: a rat ovarian cancer model. Obstet Gynecol 92:104–108

    Article  PubMed  CAS  Google Scholar 

  16. Said N, Montamed K (2005) Absence of host-secreted protein acidic and rich in cysteine (SPARC) augments peritoneal ovarian carcinomatosis. Am J Pathol 167:1739–1752

    PubMed  CAS  Google Scholar 

  17. Matsuzaki S, Canis M, Vaurs-Barrière C, Pouly JL, Boespflug-Tanguy O, Penault-Llorca F, Dechelotte P, Dastugue B, Okamura K, Mage G (2004) DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection. Mol Hum Reprod 10:719–728

    Article  PubMed  CAS  Google Scholar 

  18. Matsuzaki S, Canis M, Vaurs-Barrière C, Boespflug-Tanguy O, Dastugue B, Mage G (2005) DNA microarray analysis of gene expression in eutopic endometrium from patients with deep endometriosis using laser capture microdissection. Fertil Steril 84(Suppl 2):1180–1190

    Article  PubMed  CAS  Google Scholar 

  19. Canis M, Botchorishvili R, Wattiez A, Pouly JL, Mage G, Manhes H, Bruhat MA (2000) Cancer and laparoscopy, experimental studies: a review. Eur J Obstet Gynecol Reprod Biol 91:1–9

    Article  PubMed  CAS  Google Scholar 

  20. Arboleda MJ, Lyons JF, Kabbinavar FF, Bray MR, Snow BE, Ayala R, Danino M, Karlan BY, Slamon DJ (2003) Overexpression of AKT2/protein kinase beta leads to upregulation of beta 1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer Res 63:196–206

    PubMed  CAS  Google Scholar 

  21. Sawada K, Radjabi AR, Shinoyama N, Kistner E, Kenny H, Becker AR, Turkyilmaz MA, Salgia R, Yamada SD, Vande Woude GF, Tretiakova MS, Lengyel E (2007) c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer Res 67:1670–1679

    Article  PubMed  CAS  Google Scholar 

  22. Schmalfeldt B, Kuhn W, Reuning U, Pache L, Dettmar P, Schmitt M, Jänicke F, Höfler H, Graeff H (1995) Primary tumor and metastasis in ovarian cancer differ in their content of urokinase-type plasminogen activator, its receptor, and inhibitors types 1 and 2. Cancer Res 55:3958–3963

    PubMed  CAS  Google Scholar 

  23. Kobayashi H, Yagyu T, Kondo T, Kurita N, Inagaki K, Haruta S, Kawaguchi R, Kitanaka T, Sakamoto Y, Yamada Y, Kanayama N, Terao T (2005) Suppression of urokinase receptor expression by thalidomide is associated with inhibition of nuclear factor kappa B activation and subsequently suppressed ovarian cancer dissemination. Cancer Res 65:10464–10471

    Article  PubMed  CAS  Google Scholar 

  24. diZerega GS, Campeau JD (2001) Peritoneal repair and postsurgical adhesion formation. Hum Reprod Update 7:547–555

    Article  PubMed  CAS  Google Scholar 

  25. Hofer SO, Molema G, Hermens RA, Wanebo HJ, Reichner JS, Hoekstra HJ (1999) The effect of surgical wounding on tumour development. Eur J Surg Oncol 25:231–243

    Article  PubMed  CAS  Google Scholar 

  26. Quemener C, Gabison EE, Naïmi B, Lescaille G, Bougatef F, Podgorniak MP, Labarchède G, Lebbé C, Calvo F, Menashi S, Mourah S (2007) Extracellular matrix metalloproteinase inducer upregulates the urokinase-type plasminogen activator system promoting tumor cell invasion. Cancer Res 67:9–15

    Article  PubMed  CAS  Google Scholar 

  27. Gabison EE, Mourah S, Steinfels E, Yan L, Hoang-Xuan T, Watsky MA, De Wever B, Calvo F, Mauviel A, Menashi S (2005) Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epitheliostromal interactions and matrix metalloproteinase induction. Am J Pathol 166:209–219

    PubMed  CAS  Google Scholar 

  28. Rofstad EK, Mathiesen B, Henriksen K, Kindem K, Galappathi K (2005) The tumor bed effect: increased metastatic dissemination from hypoxia-induced upregulation of metastasis-promoting gene products. Cancer Res Mar 15(65):2387–2396

    Article  Google Scholar 

  29. Rofstad EK, Mathiesen B, Galappathi K (2004) Increased metastatic dissemination in human melanoma xenografts after subcurative radiation treatment: radiation-induced increase in fraction of hypoxic cells and hypoxia-induced upregulation of urokinase-type plasminogen activator receptor. Cancer Res 64:13–18

    Article  PubMed  CAS  Google Scholar 

  30. Hayashi M, Sakata M, Takeda T, Tahara M, Yamamoto T, Okamoto Y, Minekawa R, Isobe A, Ohmichi M, Tasaka K, Murata Y (2005) Upregulation of c-met protooncogene product expression through hypoxia-inducible factor-1 alpha is involved in trophoblast invasion under low-oxygen tension. Endocrinology 146:4682–4689

    Article  PubMed  CAS  Google Scholar 

  31. Brundell SM, Tsopelas C, Chatterton B, Touloumtzoglou J, Hewett PJ (2002) Experimental study of peritoneal blood flow and insufflation pressure during laparoscopy. Br J Surg 89:617–622

    Article  PubMed  CAS  Google Scholar 

  32. Yavuz Y, Ronning K, Lyng O, Gronbech JE, Marvik R (2003) Effect of carbon dioxide pneumoperitoneum on tissue blood flow in the peritoneum, rectus abdominis, and diaphragm muscles. Surg Endosc 17:1632–1635

    Article  PubMed  CAS  Google Scholar 

  33. Tsugawa K, Jones MK, Sugimachi K, Sarfeh IJ, Tarnawski AS (2002) Biological role of phosphatase PTEN in cancer and tissue injury healing. Front Biosci 7:e245–e251

    Article  PubMed  CAS  Google Scholar 

  34. Di Renzo MF, Olivero M, Giacomini A, Porte H, Chastre E, Mirossay L, Nordlinger B, Bretti S, Bottardi S, Giordano S, Plebani M, Gespach C, Comoglio PM (1995) Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer. Clin Cancer Res 1:147–154

    PubMed  CAS  Google Scholar 

  35. Dong G, Lee TL, Yeh NT, Geoghegan J, Van Waes C, Chen Z (2004) Metastatic squamous cell carcinoma cells that overexpress c-Met exhibit enhanced angiogenesis factor expression, scattering, and metastasis in response to hepatocyte growth factor. Oncogene 23:6199–6208

    Article  PubMed  CAS  Google Scholar 

  36. Herynk MH, Stoeltzing O, Reinmuth N, Parikh NU, Abounader R, Laterra J, Radinsky R, Ellis LM, Gallick GE (2003) Downregulation of c-Met inhibits growth in the liver of human colorectal carcinoma cells. Cancer Res 63:2990–2996

    PubMed  CAS  Google Scholar 

  37. Palmieri D, Lee JW, Juliano RL, Church FC (2002) Plasminogen activator inhibitor-1 and -3 increase cell adhesion and motility of MDA-MB-435 breast cancer cells. J Biol Chem 277:40950–40957

    Article  PubMed  CAS  Google Scholar 

  38. Xing RH, Mazar A, Henkin J, Rabbani SA (1997) Prevention of breast cancer growth, invasion, and metastasis by antiestrogen tamoxifen alone or in combination with urokinase inhibitor B-428. Cancer Res 57:3585–3593

    PubMed  CAS  Google Scholar 

  39. Xu J, Zhong Y, Weixin N, Xinyu Q, Yanhan L, Li R, Jianhua W, Zhiping Y, Jiemin C (2007) Preoperative hepatic and regional arterial chemotherapy in the prevention of liver metastasis after colorectal cancer surgery. Ann Surg 245:583–590

    Article  PubMed  Google Scholar 

  40. Mutter D, Hajri A, Tassetti V, Solis-Caxaj C, Aprahamian M, Marescaux J (1999) Increased tumor growth and spread after laparoscopy vs laparotomy: influence of tumor manipulation in a rat model. Surg Endosc 13:365–370

    Article  PubMed  CAS  Google Scholar 

  41. Raa ST, Oosterling SJ, van der Kaaij NP, van den Tol MP, Beelen RH, Meijer S, van Eijck CH, van der Sijp JR, van Egmond M, Jeekel J (2005) Surgery promotes implantation of disseminated tumor cells, but does not increase growth of tumor cell clusters. J Surg Oncol 92:124–129

    Article  PubMed  Google Scholar 

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Acknowledgments

We are indebted to all the staff in le Centre International de la Chirurgie Endoscopique (Clermont-Ferrand, France) and the technicians in the Department of Anatomie et cytologie pathologiques, CHU Clermont-Ferrand, Hôtel-Dieu for technical support. We are indebted to Karl Storz Endoscopy & GmbH (Tuttlingen, Germany) and Organon (Paris, France) for providing laparoscopic equipment and vecuronium bromide, respectively. Nicolas Bourdel is a recipient of a fellowship of the Fondation pour la Recherche Médicale (Paris, France). This study was supported in part by la Ligue Régionale de lutte contre le Cancer (Auvergne region, France).

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Authors and Affiliations

  1. Université d’Auvergne – Clermont I, Centre d′Endoscopie et des Nouvelles Techniques Interventionnelles (CENTI), Clermont-Ferrand, France

    Sachiko Matsuzaki, Nicolas Bourdel, Jean-Etienne Bazin, Jean-Luc Pouly, Gérard Mage & Michel Canis

  2. CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction, Boulevard Léon Malfreyt, 63058, Clermont-Ferrand Cédex, France

    Sachiko Matsuzaki, Nicolas Bourdel, Jean-Luc Pouly, Gérard Mage & Michel Canis

  3. CHU Clermont-Ferrand, Hôtel-Dieu, Service d’Anatomie et Cytologie Pathologiques, Clermont-Ferrand, France

    Claude Darcha & Pierre J. Déchelotte

  4. CHU Clermont-Ferrand, Hôtel Dieu, Service d’Anesthésie Réanimation, Clermont-Ferrand, France

    Jean-Etienne Bazin

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  1. Sachiko Matsuzaki
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  2. Nicolas Bourdel
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  7. Gérard Mage
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Correspondence to Sachiko Matsuzaki.

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Matsuzaki, S., Bourdel, N., Darcha, C. et al. Molecular mechanisms underlying postoperative peritoneal tumor dissemination may differ between a laparotomy and carbon dioxide pneumoperitoneum: a syngeneic mouse model with controlled respiratory support. Surg Endosc 23, 705–714 (2009). https://doi.org/10.1007/s00464-008-0041-7

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  • DOI: https://doi.org/10.1007/s00464-008-0041-7

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