Inhibitory Effects of Dunning Rat Prostate Tumor Fluid on Proliferation of the Metastatic MAT-LyLu Cell Line

  • Bugan, Ilknur ;
  • Altun, Seyhan
  • Published : 2015.02.25


Tumor fluid accumulation occurs in both human cancer and experimental tumor models. Solid tumors show a tendency to tumor fluid accumulation because of their anatomical and physiological features and this may be influenced by molecular factors. Fluid accumulation in the peri-tumor area also occurs in the Dunning model of rat prostate cancer as the tumor grows. In this study, the effects of tumor fluids that were obtained from Dunning prostate tumor-bearing Copenhagen rats on the strongly metastatic MAT-LyLu cell line were investigatedby examining the cell's migration and tumor fluid's toxicity and the kinetic parameters such as cell proliferation, mitotic index, and labelling index. In this research, tumor fluids were obtained from rats injected with $2{\times}10^5$ MAT-LyLu cells and treated with saline solution, and 200 nM tetrodotoxin (TTX), highly specific sodium channel blocker was used. Sterilized tumor fluids were added to medium of MAT-LyLu cells with the proportion of 20% in vitro. Consequently, it was demonstrated that Dunning rat prostate tumor fluid significantly inhibited proliferation (up to 50%), mitotic index, and labeling index of MAT-LyLu cells (up to 75%) (p<0.05) but stimulated the motility of the cells in vitro.


Dunning prostate tumor;MAT-LyLu cells;Copenhagen rats;tumor fluid;in vitro


  1. Baggenstos MA, Butman JA, Oldfield EH, et al (2007). Role of edema in peritumoral cyst formation. Neurosurg Focus, 22, 9.
  2. Boucher Y, Baxter LT, Jain RK (1990). Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: Implications for therapy, Cancer Res, 50, 4478-84.
  3. Davidson B, Elstrand MB, McMaster MT, et al (2005). HLA-G expression in effusions is a possible marker of tumor susceptibility to chemotherapy in ovarian carcinoma. Gynecol Oncol, 96, 42-7.
  4. Donenko FV, Kabieva AO, Moroz LV (1992). The effect of ascitic fluid on the growth of Ehrlich tumor and Lewis carcinoma. Bulleten Eksperimentalnoi Biologii I Meditsiny, 114, 191-3.
  5. Du K, Gong HY, Gong ZM (2014). Influence of serum VEGF levels on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer. Asian Pac J Cancer Prev, 15, 8793-6.
  6. Evans CP, Walsh DS, Kohn EC (1991). An autocrine motility factor secreted by the Dunning R-3327 rat prostatic adenocarcinoma cell subtype AT2.1. Int J Cancer, 49, 109-13.
  7. Fraser SP, Salvador V, Manning EA, et al (2003). Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility. J Cell Physiol, 195, 479-87.
  8. Fukumura D, Jain RK (2007a). Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization, Microvascular Res, 74, 72-84.
  9. Fukumura D, Jain RK (2007b). Tumor microenvironment abnormalities: causes, consequenses, and strategies to normalize, J Cellular Biochemistry, 101, 937-49.
  10. Funasaka T, Haga A, Raz A, et al (2002).Tumor autocrine motility factor induces hyperpermeability of endothelial and mesothelial cells leading to accumulation of ascites fluid. Biochem Biophys Res Comm, 293, 192-200.
  11. Funasaka T, Haga A, Raz A, et al (2001).Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility, Biochem Biophys Res Comm, 285, 118-28.
  12. Funasaka T, Yanagawa T, Hogan V, et al (2005). Autocrine motility factor possesses a possibility of developing a new target for anti-cancer treatment. Current Cancer Therapy Reviews, 1, 187-97.
  13. Grimes JA, Fraser SP, Stephens GJ, et al (1995). Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro. FEBS Letters, 369, 290-4.
  14. Amirhofran Z, Sheikhi AK, Kumar PV, et al (2002). Soluble HLA class I molecules in malignant pleural and peritoneal effusions and its possible role on NK and LAK cytotoxicity, J Cancer Res Clin Oncol, 128, 443-8.
  15. Badawi AF (2000).The role of prostaglandin synthesis in prostate cancer. British J Urol, 85, 451-62.
  16. Han T, Kang D, Ji D, et al (2013). How does cancer cell metabolism affect tumor migration and invasion? Cell Adh Migration, 7, 395-403.
  17. Harizi H, Corcuff JB, Gulade N (2008). Arachidonic-acidderived eicosanoids: roles in biology and immunopathology, Trends Molecular Med, 14, 461-9.
  18. Heldin C, Rubin K, Pietras K, et al (2004). High interstitial fluid pressure-an obstacle in cancer therapy, Nature Rev, 4, 806-13.
  19. Hompland T, Ellingsen C, Ovrebo KM, et al (2012). Interstitial fluid pressure and associated lymph node metastasis revealed in tumors by dynamic contrast-enhanced MRI, Cancer Res, 72, 4899-908.
  20. Huang Z, Zhang N, Zha L, et al (2014). Aberrant expression of the autocrine motility factor receptor correlates with poor prognosis and promotes metastasis in gastric carcinoma, Asian Pac J Cancer Prev, 15, 989-97.
  21. Inan I, de Sousa S, Myers PO, et al (2008). Management of malignant pleural effusion and ascites by a triple access multi perforated large diameter catheter port system, World J Surg Oncology, 18, 85.
  22. Kagi D, Vignaux F, Ledermann B, et al (1994). Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Sci, 265, 528-30.
  23. Kohn EC, Travers LA, Kassis J, et al (2005). Malignant effusions are sources of fibronectin and other promigratory and proinvasive components. Diagnostic Cytopathology, 33, 300-8.
  24. Kraft A, Weindel K, Ochs A, et al (1999).Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer, 85, 178-87.<178::AID-CNCR25>3.0.CO;2-7
  25. Lazebnik YA, Medvedeva ND, Zenin VV (1991). Reversible G2 block in the cell cycle of Ehrlich ascites carcinoma cells. Experimental Cell Res, 195, 247-54.
  26. Lonser RR, Vortmeyer AO, Butman JA, et al (2005). Edema is a precursor to central nervous system peritumoral cyst formation. Ann Neurol, 58, 392-9.
  27. Lunt SJ, Chaudary N, Hill RP. (2009). The Tumor microenvironment and metastatic disease, Clinic and Experimental Metastasis, 26(1):19-34.
  28. Milosevic M, Fyles A, Hedley D, et al (2001). Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res, 61, 6400-5.
  29. Mitani K, Nishioka Y, Yamabe K, et al (2003). Soluble Fas in malignant pleural effusion and its expression in lung cancer cells. Cancer Sci, 94, 302-7.
  30. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunological Methods, 65, 55-63.
  31. Munson JM, Shieh AC (2014). Interstitial fluid flow in cancer: implications for disease progression and treatment. Cancer Manag Res, 6, 317-28.
  32. Rishikesh MK, Sadhana SS (2003). Prostaglandins and cyclooxygenase: Their probable role in cancer, Indian J Pharmacol, 35, 3-12.
  33. Rofstad EK, Galappathi K, Mathiesen BS (2014).Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular density, and lymph node metastasis. Neoplasia, 16, 586-94.
  34. Rouas-freiss N, Moreau P, Ferrone S, et al (2005). HLA-G proteins in cancer: do they provide tumor cells with an escape mechanism? Cancer Res, 65, 10139-44.
  35. Salnikov AV, Iversen VV, Koisti M, et al (2003). Lowering of tumor interstitial fluid pressure specifically augments efficacy of chemotherapy. Federat Am Soc Experimental Biology J, 17, 1756-1758.
  36. Shaw MW, Ablin RJ, Ray P, et al (1985). Immunobiology of the Dunning R-3327 rat prostate adenocarcinoma sublines: plasma and tumor effusion prostaglandins. Am J Reproductive Immunology Microbiology, 8, 77-9.
  37. Singer G, Rebmann V, Chen YC, et al (2003). HLA-G is a potential tumor marker in malignant ascites, Clin Cancer Res, 9, 4460-4.
  38. Thongchot S, Yongvanit P, Loilome W, et al (2014). High expression of HIF-$1\alpha$, BNIP3 and PI3KC3: hypoxia-induced autophagy predicts cholangiocarcinoma survival and metastasis. Asian Pac J Cancer Prev, 15, 5873-8.
  39. Wilson EM, French FS, Petrusz P (1982). Transferrin in the rat prostate Dunning tumor. Cancer Res, 42, 243-51.
  40. Yildirim S, Altun S, Gumushan H, et al (2012). Voltage-gated sodium channel activity promotes prostate cancer metastasis in vivo. Cancer Letters, 323, 58-61.
  41. Zar JH (1999). Bioistatistical analysis, 4th ed., prentice hall international Inc., New Jersey.