Abstract
Objective
To evaluate the influence of intraperitoneal treatment with phospholipids on the formation of peritoneal carcinosis after inoculation of colonic tumor cells in rats.
Summary background data
The presence of tumor cells in the peritoneal cavity serves as a prognostic marker for postoperative survival after resection of gastrointestinal cancer. Intraperitoneal tumor cell attachment is a pivotal step in developing peritoneal carcinosis. Intraabdominal application of phospholipids resulted in a significant decrease of adhesion formation, especially at sites of peritoneal lesions.
Methods
2×106 colonic tumor cells (DHD/K12/TRb) were injected intraperitonely in female BD-IX rats. A total of 90 rats were divided into three groups with treatments of phospholipids at 75 mg/kg or 150 mg/kg bodyweight or sodium chloride at 0.9% in the control group. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of tumor attachment and the Peritoneal Cancer Index. Over a 90-day observation period, the survival rate was analyzed. In vitro, we examined the reduction of tumor cell adhesion on extracellular matrix components after treatment with phospholipids. Microtiter plates were coated with laminin, fibronectin or collagen IV for adhesion experiments.
Results
In our study, we found a significant reduction of peritoneal dissemination with respect to all evaluation methods after treatment with phospholipids at 150 mg/kg in animals without peritoneal lesions. This could not be achieved using the lower concentration of phospholipids (75 mg/kg). In vitro, the maximum reductions of tumor cell adhesion by phospholipids compared with the control values for laminin and fibronectin were 46% and 37%, respectively, whereas for collagen IV the reduction was only 24% (p<0.0001).
Conclusions
A new method of prevention of intraperitoneal tumor cell adhesion, possibly leading to a reduced incidence of peritoneal carcinosis after surgery of gastrointestinal tumors, is introduced.
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References
Boku T, Nakane Y, Minoura T, Takada H, Yamamura M, Hioki K, Yamamoto M (1990) Prognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer. Br J Surg 77:436–439
Jansen M, Buchin P, Dreuw B, Fass J, Minkenberg R, Mehring M, Schumpelick V (2001) Prognostic factors for development of peritoneal carcinosis in stomach carcinoma. Chirurg 72:561–565
Koga S, Kaibara N, Iitsuka Y, Kudo H, Kimura A, Hiraoka H (1984) Prognostic significance of intraperitoneal free cancer cells in gastric cancer patients. J Cancer Res Clin Oncol 108:236–238
Schott A, Vogel I, Krueger U, Kalthoff H, Schreiber HW, Schmiegel W, Henne-Bruns D, Kremer B, Juhl H (1998) Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker. Ann Surg 227:372–379
Bando E, Yonemura Y, Takeshita Y, Taniguchi K, Yasui T, Yoshimitsu Y, Fushida S, Fujimura T, Nishimura G, Miwa K (1999) Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma. Am J Surg 178:256–262
Broll R, Lembcke K, Stock C, Zingler M, Duchrow M, Schimmelpenning H, Strik M, Muller G, Kujath P, Bruch HP (1996) 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
Hagiwara A, Takahashi T, Ueda T, Lee R, Takeda M, Itoh T (1988) Intraoperative chemotherapy with carbon particles adsorbing mitomycin C for gastric cancer with peritoneal dissemination in rabbits. Surgery 104:874–881
Fass J, Jansen M, Zengel K, Reinecke T, Asshoff G, Schumpelick V (1998) Results of intraperitoneal active charcoal-mitomycin C therapy of stomach carcinoma with serosa invasion. Langenbecks Arch Chir Suppl Kongressbd 115:1363–1366
Sayag AC, Gilly FN, Carry PY, Perdrix JP, Panteix G, Brachet A, Banssillon V, Braillon G (1993) Intraoperative chemohyperthermia in the management of digestive cancers. A general review of literature. Oncology 50:333–337
Fujimura T, Yonemura Y, Fujita H, Michiwa Y, Kawamura T, Nojima N, Sato T, Fushida S, Nishimura G, Miwa K, Miyazaki I, Murakami K, Katayama K, Yamaguchi A (1999) Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies. Int Surg 84:60–66
Fujimoto S, Shrestha RD, Kokubun M, Kobayashi K, Kiuchi S, Konno C, Ohta M, Takahashi M, Kitsukawa Y, Mizutani M (1990) Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer. Ann Surg 212:592–596
Koga S, Hamazoe R, Maeta M, Shimizu N, Murakami A, Wakatsuki T (1988) Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C. Cancer 61:232–237
Schwartz GK (1996) Invasion and metastases in gastric cancer: in vitro and in vivo models with clinical correlations. Semin Oncol 23:316–324
Yashiro M, Chung YS, Nishimura S, Inoue T, Sowa M (1996) Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as “soil” for peritoneal dissemination. Cancer 77:1668–1675
Nakashio T, Narita T, Akiyama S, Kasai Y, Kondo K, Ito K, Takagi H, Kannagi R (1997) Adhesion molecules and TGF-beta1 are involved in the peritoneal dissemination of NUGC-4 human gastric cancer cells. Int J Cancer 70:612–618
Hagiwara A, Sawai K, Sakakura C, Shirasu M, Ohgaki M, Imanishi T, Yamasaki J, Togawa T, Takahashi T (1997) Prevention of peritoneal metastasis of cancer with dextran sulfate—an experimental study in mice. Anticancer Drugs 8:894–897
Haverlag R, van Rossen ME, van den Tol MP, Bonthuis F, Marquet RL, Jeekel J (1999) Hyaluronate-based coating solution for prevention of surgical adhesions has no major effect on adhesion and growth of intraperitoneal tumour cells. Eur J Surg 165:791–795
Muller SA, Treutner KH, Tietze L, Anurov M, Titkova S, Polivoda M, Oettinger AP, Schumpelick V (2001) Efficacy of adhesion prevention and impact on wound healing of intraperitoneal phospholipids. J Surg Res 96:68–74
Muller SA, Treutner KH, Tietze L, Anurov M, Titkova S, Polivoda M, Oettinger AP, Schumpelick V (2001) Influence of intraperitoneal phospholipid dosage on adhesion formation and wound healing at different intervals after surgery. Langenbecks Arch Surg 386:278–284
Garcia-Olmo D, Garcia-Rivas M, Garcia-Olmo DC, Atienzar M (1998) Orthotopic implantation of colon carcinoma cells provides an experimental model in the rat that replicates the regional spreading pattern of human colorectal cancer. Cancer Lett 132:127–133
Treutner KH, Bertram P, Lerch MM, Klimaszewski M, Petrovic-Kallholm S, Sobesky J, Winkeltau G, Schumpelick V (1995) Prevention of postoperative adhesions by single intraperitoneal medication. J Surg Res 59:764–771
Sugarbaker PH (1996) Peritoneal carcinomatosis: natural history and rational therapeutic interventions using intraperitoneal chemotherapy. Cancer Treat Res 81:149–168
Tietze L, Borntraeger J, Klosterhalfen B, Amo-Takyi B, Handt S, Gunther K, Merkelbach-Bruse S (1999) Expression and function of beta(1) and beta(3) integrins of human mesothelial cells in vitro. Exp Mol Pathol 66:131–139
Aumailley M, Mann K, von der MH, Timpl R (1989) Cell attachment properties of collagen type VI and Arg-Gly-Asp dependent binding to its alpha 2(VI) and alpha 3(VI) chains. Exp Cell Res 181:463–474
Dunnington DJ, Buscarino C, Gennaro D, Greig R, Poste G (1987) Characterization of an animal model of metastatic colon carcinoma. Int J Cancer 39:248–254
Reisser D, Fady C, Lagadec P, Martin F (1991) Influence of the injection site on the tumorigenicity of a cloned colon tumor cell line in the rat. Bull Cancer 78:249–252
Qin Y, Schally AV, Willems G (1991) Somatostatin analogue RC-160 inhibits the growth of transplanted colon cancer in rats. Int J Cancer 47:765–770
Hagiwara A, Sakakura C, Yamasaki J, Togawa T, Sonoyama Y, Fujiyama J, Yamagishi H (2000) Dextran sulfate inhibits injured abdominal wall-specific tumor implantation in mice. Anticancer Drugs 11:873–877
Hagiwara A, Sakakura C, Shirasu M, Togawa T, Sonoyama Y, Fujiyama J, Ebihara Y, Itoh T, Yamagishi H (2000) Intraperitoneal 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
diZerega GS (1996) Use of adhesion prevention barriers in ovarian surgery, tubalplasty, ectopic pregnancy, endometriosis, adhesiolysis, and myomectomy. Curr Opin Obstet Gynecol 8:230–237
Treutner KH, Schumpelick V (2000) Prevention of adhesions. Wish and reality. Chirurg 71:510–517
Tan B, Wang JH, Wu QD, Kirwan WO, Redmond HP (2001) Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo. Br J Surg 88:246–250
Muller SA, Treutner KH, Tietze L, Jansen M, Anurov M, Titkova S, Oettinger AP, Schumpelick V (2002) Influence of early drainage of intraperitoneal phospholipids on efficacy of adhesion prevention. J Invest Surg 15:23–28
van den Tol MP, Haverlag R, van Rossen ME, Bonthuis F, Marquet RL, Jeekel J (2001) Glove powder promotes adhesion formation and facilitates tumour cell adhesion and growth. Br J Surg 88:1258–1263
Beavis J, Harwood JL, Coles GA, Williams JD (1994) Synthesis of phospholipids by human peritoneal mesothelial cells. Perit Dial Int 14:348–355
Chailley-Heu B, Rubio S, Rougier JP, Ducroc R, Barlier-Mur AM, Ronco P, Bourbon JR (1997) Expression of hydrophilic surfactant proteins by mesentery cells in rat and man. Biochem J 328(Pt 1):251–256
Hakomori S, Zhang Y (1997) Glycosphingolipid antigens and cancer therapy. Chem Biol 4:97–104
Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25
Hauptmann S, Denkert C, Lohrke H, Tietze L, Ott S, Klosterhalfen B, Mittermayer C (1995) Integrin expression on colorectal tumor cells growing as monolayers, as multicellular tumor spheroids, or in nude mice. Int J Cancer 61:819–825
Schreiner C, Bauer J, Margolis M, Juliano RL (1991) Expression and role of integrins in adhesion of human colonic carcinoma cells to extracellular matrix components. Clin Exp Metastasis 9:163–178
Lotz MM, Korzelius CA, Mercurio AM (1990) Human colon carcinoma cells use multiple receptors to adhere to laminin: involvement of alpha 6 beta 4 and alpha 2 beta 1 integrins. Cell Regul 1:249–257
Martin-Padura I, Bazzoni G, Zanetti A, Bernasconi S, Elices MJ, Mantovani A, Dejana E (1994) A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered by beta 1 integrin chain. J Biol Chem 269:6124–6132
Wilson JR, Weiser MM (1992) Colonic cancer cell (HT29) adhesion to laminin is altered by differentiation: adhesion may involve galactosyltransferase. Exp Cell Res 201:330–334
Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71:1368–1383
Acknowledgments
This work was supported by Fresenius Kabi, Bad Homburg, Germany. Permission of local authorities: file number AZ50.203.2-AC 18, 44/00.
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Jansen, M., Treutner, KH., Lynen Jansen, P. et al. Phospholipids reduce the intraperitoneal adhesion of colonic tumor cells in rats and adhesion on extracellular matrix in vitro. Int J Colorectal Dis 19, 525–532 (2004). https://doi.org/10.1007/s00384-004-0611-7
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DOI: https://doi.org/10.1007/s00384-004-0611-7