Skip to main content

Advertisement

SpringerLink
Log in

Inhibition of Gastric Cancer Cell Adhesion in Nude Mice by Inraperitoneal Phospholipids

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Adhesion of tumor cells to mesothelial cells or extracellular matrix components is a pivotal step in developing peritoneal dissemination after gastric cancer. As phospholipids were found to reduce adhesion formation, especially at sites of peritoneal lesions, we assessed the inhibition of attachment of NUGC-4 gastric cancer cells by local treatment with phospholipids to the peritoneum in nude mice. Gastric cancer cells (1×l06) suspended in either normal saline (controls) or phospholipid suspension 75 mg/kg body weight (PL75) or 150 mg/kg (PL150) were injected intraperitoneally into 90 female BALB/c nu/nu mice. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days the extent of peritoneal carcinosis and the Peritoneal Cancer Index were evaluated. Statistical analysis was performed with two factorial ANOVAs. The level of significance was adjusted according to Bonferrorni (α = 0.00278). During a 90-day observation period the survival rate was determined using the log rank test.

After 30 days the intraperitoneal tumor volume was reduced by PL150 up to 0.6 ml (SEM 0.16) and 0.48 ml (SEM 0.09) in mice with peritoneal lesions compared to 0.9 ml (SEM 0.2) and 0.9 ml (SEM 0.1) in the control group (P = 0.04). The mean area of tumor adhesion amounted to 145 mm2 (SEM 17) (P = 0.08) and 164 mm2 (SEM 32.8) (P = 0.049) with peritoneal lesions after treatment with PL150 [controls: 216 mm2 (SEM 28.5) and 245 mm2 (SEM 29.3)]. The peritoneal cancer index was 16.4 (SEM 1.7) in the control group and 9 (SEM 1.68) with PL150 (P = 0.0002). In the subgroup with peritoneal lesions, the respective values were as follows: controls: 20.8 (SEM 0.85); PL 150:14.3 (SEM 1.07) (P = 0.0001). We found a prolonged survival rate after treatment with PL150. However, this effect was not significantly different to that seen in the control group. Treatment with PL75 had no significant influence. Phospholipids may be an efficacious and economic tool for reducing peritoneal tumor cell adhesion and consequently the development of peritoneal carcinosis after resection of gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • T Boku Y Nakane T Minoura et al. (1990) ArticleTitlePrognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer Br. J. Surg. 77 436–439 Occurrence Handle2340396

    PubMed  Google Scholar 

  • M Jansen P Buchin B Dreuw et al. (2001) ArticleTitle[Prognostic factors for development of peritoneal carcinosis in stomach carcinoma] ]Chirurg 72 561–565 Occurrence Handle10.1007/s001040051346 Occurrence Handle11383068

    Article  PubMed  Google Scholar 

  • S Koga N Kaibara Y Iitsuka et al. (1984) ArticleTitlePrognostic significance of intraperitoneal free cancer cells in gastric cancer patients J. Cancer Res. Clin. Oncol. 108 236–238 Occurrence Handle10.1007/BF00402474 Occurrence Handle6470030

    Article  PubMed  Google Scholar 

  • A Schott I Vogel U Krueger et al. (1998) ArticleTitleIsolated tumor cells are frequently detectable in the peritoneal, cavity of gastric and colorgctal cancer patients and serve as a new prognostic marker Ann. Surg. 227 372–379 Occurrence Handle10.1097/00000658-199803000-00009 Occurrence Handle9527060

    Article  PubMed  Google Scholar 

  • E Bando Y Yonemura Y Takeshita et al. (1999) ArticleTitleIntraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma Am. J. Surg. 178 256–262 Occurrence Handle10.1016/S0002-9610(99)00162-2 Occurrence Handle10527450

    Article  PubMed  Google Scholar 

  • R Broll K Lembcke C Stock et al. (1996) ArticleTitle[Tumor cell dissemination in bone marrow and peritoneal cavity: an immunocytochemical study of patients with stomach or colorectal carcinoma] Langenbecks Arch. Chir. 381 51–58

    Google Scholar 

  • Y Kiyasu S Kaneshima S. Koga (1981) ArticleTitleMorphogenesis of peritoneal metastasis in human gastric cancer Cancer Res. 41 1236–1239 Occurrence Handle7459864

    PubMed  Google Scholar 

  • S Koga H Kudo Y Kiyasu et al. (1980) ArticleTitleA scanning electron microscopic study on the peritoneal implantation of ascites hepatoma AH100B cells in rats Gann 71 8–13 Occurrence Handle7380138

    PubMed  Google Scholar 

  • GK Schwartz (1996) ArticleTitleInvasion and metastases in gastric cancer: in vitro and in vivo models with clinical correlations Semin. Oncol. 23 316–324 Occurrence Handle8658215

    PubMed  Google Scholar 

  • M Yashiro YS Chung S Nishimura et al. (1996) ArticleTitleFibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as “soil” for peritoneal dissemination Cancer 77 1668–1675 Occurrence Handle8608560

    PubMed  Google Scholar 

  • GP Gui JR Puddefoot GP Vinson et al. (1995) ArticleTitleIn vitro regulation of human breast cancer cell adhesion and invasion via integrin receptors to the extracellular matrix Br. J. Surg. 82 1192–1196 Occurrence Handle7551993

    PubMed  Google Scholar 

  • T Nakashio T Narita S Akiyama et al. (1997) ArticleTitleAdhesion molecules and TGF-beta1 are involved in the peritoneal dissemination of NUGC-4 human gastric cancer cells Int. J. Cancer 70 612–618 Occurrence Handle10.1002/(SICI)1097-0215(19970304)70:5<612::AID-IJC20>3.0.CO;2-D Occurrence Handle9052764

    Article  PubMed  Google Scholar 

  • A Hagiwara K Sawai C Sakakura et al. (1997) ArticleTitlePrevention of peritoneal metastasis of cancer with dextran sulfate—an experimental study in mice Anticancer Drugs 8 894–897 Occurrence Handle9402317

    PubMed  Google Scholar 

  • R Haverlag ME Rossen Particlevan MP Tol Particlevan den et al. (1999) ArticleTitleHyaluronate-based coating solution for prevention of surgical adhesions has no major and growth of intraeritoneal tumor cells Eur. J. Surg. 165 791–795 Occurrence Handle10.1080/11024159950189609 Occurrence Handle10494648

    Article  PubMed  Google Scholar 

  • J Beavis JL Harwood GA Coles et al. (1994) ArticleTitleSynthesis of phospholipids by human peritoneal mesothelial cell Perit. Dial. Int. 14 348–355 Occurrence Handle7827184

    PubMed  Google Scholar 

  • B Chailley-Heu S Rubio JP Rougier et al. (1997) ArticleTitleExpression of hydrophilic surfactant proteins by mesentery cells in rat and man Biochem. J. 328 251–256 Occurrence Handle9359861

    PubMed  Google Scholar 

  • S Hakomori (2003) ArticleTitleStructure, organization, and function of glycosphingolipids in membrane Curr. Opin. Hematol. 10 16–24 Occurrence Handle10.1097/00062752-200301000-00004 Occurrence Handle12483107

    Article  PubMed  Google Scholar 

  • SA Muller KH Treutner L Tietze et al. (2001) ArticleTitleEfficacy of adhesion prevention and impact on wound healing of intraperitoneal phospholipids J. Surg. Res. 96 68–74 Occurrence Handle10.1006/jsre.2000.6031 Occurrence Handle11180998

    Article  PubMed  Google Scholar 

  • SA Muller KH Treutner L Tietze et al. (2001) ArticleTitleInfluence of intraperitoneal phospholipid dosage on adhesion formation and wound healing at different intervals after surgery Langenbecks Arch. Surg. 386 278–284 Occurrence Handle10.1007/s004230100212 Occurrence Handle11466570

    Article  PubMed  Google Scholar 

  • S Akiyama H Amo T Watanabe et al. (1988) ArticleTitleCharacteristics of three human gastric cancer cell lines, NU-GC-2, NU-GC-3 and NU-GC-4 Jpn. J. Surg. 18 438–446 Occurrence Handle3172586

    PubMed  Google Scholar 

  • CL Schreiner M Fisher J Bauer et al. (1995) ArticleTitleDefective vasculature in fibronectin-receptor-deficient CHO cell tumors in nude mice Int. J. Cancer 55 436–441

    Google Scholar 

  • KH Treutner P Bertram MM Lerch et al. (1995) ArticleTitlePrevention of postoperative adhesions by single intraperitoneal medication J. Surg. Res. 59 764–771 Occurrence Handle10.1006/jsre.1995.1237 Occurrence Handle8538179

    Article  PubMed  Google Scholar 

  • PH Sugarbaker (1999) ArticleTitleManagement of peritoneal-surface malignancy: the surgeon’s role. Langenbecks Arch. Surg. 384 576–587 Occurrence Handle10.1007/s004230050246

    Article  Google Scholar 

  • PH Sugarbaker (1996) ArticleTitlePeritoneal carcinomatosis: natural history and rational therapeutic interventions using intraperitoneal chemotherapy Cancer Treat. Res. 81 149–168 Occurrence Handle8834582

    PubMed  Google Scholar 

  • MP Tol ParticleVan den R Haverlag ME Rossen Particlevan et al. (2001) ArticleTitleGlove powder promotes adhesion formation and facilitates tumor cell adhesion and growth” Br. J. Surg. 88 1258–1263 Occurrence Handle10.1046/j.0007-1323.2001.01846.x Occurrence Handle11531877

    Article  PubMed  Google Scholar 

  • PM Tol ParticleVan den EE Rossen Particlevan CH Eijck Particlevan et al. (1998) ArticleTitleReduction of peritoneal trauma by using nonsurgical gauze leads to less implantation metastasis of spilled tumor cells Ann. Surg. 227 242–248 Occurrence Handle10.1097/00000658-199802000-00014 Occurrence Handle9488523

    Article  PubMed  Google Scholar 

  • T Satta M Yamauchi K Isobe et al. (1993) ArticleTitleEstablishment of an in vivo cloning system for human gastric cancer Gastroenterol. Jpn. 28 580 Occurrence Handle8397134

    PubMed  Google Scholar 

  • B Tan JH Wang QD Wu et al. (2001) ArticleTitleSodium hyaluronate enhances colorectal tumor cell metastatic potential in vitro and in vivo Br. J. Surg. 88 246–250 Occurrence Handle10.1046/j.1365-2168.2001.01664.x Occurrence Handle11167875

    Article  PubMed  Google Scholar 

  • A Hagiwara C Sakakura J Yamasaki et al. (2000) ArticleTitleDextran sulfate inhibits injured abdominal wall-specific tumor implantation in mice Anticancer Drugs 11 873–877 Occurrence Handle10.1097/00001813-200011000-00012 Occurrence Handle11142696

    Article  PubMed  Google Scholar 

  • A Hagiwara C Sakakura M Shirasu et al. (2000) ArticleTitleIntraperitoneal injection of dextran sulfate as an anti-adherent drug for the prevention of peritoneal metastasis of cancer shows low toxicity in animals Anticancer Drugs 11 393–399 Occurrence Handle10.1097/00001813-200006000-00010 Occurrence Handle10912956

    Article  PubMed  Google Scholar 

  • GS DiZerega (1996) ArticleTitleUse of adhesion prevention barriers in ovarian surgery, tubalplasty, ectopic pregnancy, endometriosis, adhesiolysis, and myomectomy Curr. Opin. Obstet. Gynecol. 8 230–237 Occurrence Handle8818536

    PubMed  Google Scholar 

  • KH Treutner V Schumpelick (2000) ArticleTitle[Prevention of adhesions: Wish and reality] Chirurg 71 510–517 Occurrence Handle10.1007/s001040050848 Occurrence Handle10875006

    Article  PubMed  Google Scholar 

  • SK Akiyama K Nagata KM Yamada (1990) ArticleTitleCell surface receptors for extracellular matrix components Biochim. Biophys. Acta 91 91–110

    Google Scholar 

  • RO Hynes (1992) ArticleTitleIntegrins: versatility, modulation, and signaling in cell adhesion Cell 69 11–25 Occurrence Handle10.1016/0092-8674(92)90115-S Occurrence Handle1555235

    Article  PubMed  Google Scholar 

  • AP Mould JA Askari S Aota et al. (1997) ArticleTitleDefining the topology of integrin alpha5beta1-fibronectin interactions using inhibitory anti-alpha5 and anti-beta1 monoclonal antibodies. Evidence that the synergy sequence of fibronectin is recognized by the amino-terminal repeats of the alpha5 subunit” J. Biol. Chem. 272 17283–17292 Occurrence Handle10.1074/jbc.272.28.17283 Occurrence Handle9211865

    Article  PubMed  Google Scholar 

  • AP Mould JA Askari SK Akiyama et al. (1991) ArticleTitleAn assessment of the efficacy of anti-integrin alpha subunit monoclonal antibody production using affinity purified beta 1-integrin dimers as immunogen Biochem. Soc. Trans. 19 361S Occurrence Handle1794496

    PubMed  Google Scholar 

  • KM Yamada DW Kennedy SS Yamada et al. (1990) ArticleTitleMonoclonal antibody and synthetic peptide inhibitors of human tumor cell migration Cancer Res. 50 4485–4496 Occurrence Handle2369727

    PubMed  Google Scholar 

  • KR Gehlsen WS Argraves MD Pierschbacher et al. (1988) ArticleTitleInhibition of in vitro tumor cell invasion by Arg-Gly-Asp-containing synthetic peptides J. Cell Biol. 106 925–930 Occurrence Handle10.1083/jcb.106.3.925 Occurrence Handle2450101

    Article  PubMed  Google Scholar 

  • J Haier M Nasralla GL Nicolson (1999) ArticleTitleInfluence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen Int. J. Colorectal Dis. 14 119–127 Occurrence Handle10.1007/s003840050196 Occurrence Handle10367258

    Article  PubMed  Google Scholar 

  • CA Jacobi FJ Peter FA Wenger et al. (1999) ArticleTitleNew therapeutic strategies to avoid intra- and extraperitoneal metastases during laparoscopy: results of a tumor model in the rat Dig. Surg. 16 393–399 Occurrence Handle10.1159/000018754 Occurrence Handle10567800

    Article  PubMed  Google Scholar 

  • J Dennis C Waller R Timpl et al. (1982) ArticleTitleSurface sialic acid reduces attachment of metastatic tumor cells to collagen type IV and fibronectin Nature 300 274–276 Occurrence Handle10.1038/300274a0 Occurrence Handle7144883

    Article  PubMed  Google Scholar 

  • BA. Hills (1992) ArticleTitleGraphite-like lubrication of mesothelium by oligolamellar pleural surfactant J. Appl. Physiol. 73 1034–1039 Occurrence Handle1400014

    PubMed  Google Scholar 

  • SA Muller KH Treutner M Anurov et al. (2003) ArticleTitleExperimental evaluation of phospholipids and icodextrin in re-formation of peritoneal adhesions Br. J. Surg. 90 1604–1607 Occurrence Handle10.1002/bjs.4316 Occurrence Handle14648743

    Article  PubMed  Google Scholar 

  • M Jansen KH Treutner JP Lynen et al. (2004) ArticleTitlePhospholipids reduce the intraperitoneal adhesion of colonic tumor cells in rats and adhesion on extracellular matrix in vitro Int. J. Colorectal Dis. 19 525–532 Occurrence Handle10.1007/s00384-004-0611-7 Occurrence Handle15309464

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The work was supported by Fresenius Kabi, Bad Homburg, Germany and by grants from the Deutsche Forschungsgesellschaft (DFG, JA 1123/1-1). Permission of local authorities; File number AZ50.203.2-AC 18,44/00.

Author information

Authors and Affiliations

  1. Department of Surgery, University Clinic, RWTH Aachen Pauwelsstrasse 30, Aachen, 52057, Germany

    Marc Jansen M.D., Karl-Heinz Treutner M.D., Sebastian Zuber, Jens Otto & Volker Schumpelick M.D.

  2. Interdisciplinary Center of Clinical Research (IZKF) Biomat, University Clinic, RWTH Aachen Pauwelsstrasse 30, Aachen, 52057, Germany

    Petra Lynen Jansen M.D.

  3. Insitute of Pathology, University Clinic, RWTH Aachen Pauwelsstrasse 30, Aachen, 52057, Germany

    Lothar Tietze M.D.

Authors
  1. Marc Jansen M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karl-Heinz Treutner M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Petra Lynen Jansen M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sebastian Zuber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jens Otto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lothar Tietze M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Volker Schumpelick M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marc Jansen M.D..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jansen, M., Treutner, KH., Jansen, P.L. et al. Inhibition of Gastric Cancer Cell Adhesion in Nude Mice by Inraperitoneal Phospholipids. World J. Surg. 29, 708–714 (2005). https://doi.org/10.1007/s00268-005-7583-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-005-7583-9

Keywords

Search

Navigation