Skip to main content
Log in

Effect of IL-6 on tumor cell invasion of vascular endothelial monolayers

  • Original Articles
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

The effect of interleukin-6 (IL-6) on the invasive capacity of B16-F1 mouse melanoma cells into vascular endothelial monolayers was examined, and an in vitro assay system for the quantitative determination of tumor cell invasiveness, using confocal microscopy with a fluorescence image analyzer, was developed. First, the invasive capacity of B16-F1 mouse melanoma cells against bovine vascular endothelial monolayers was estimated; then, the gap junctional intercellular communication (GJIC) of endothelial cells was examined. Treatment of endothelial cells with IL-6 resulted in a remarkable increase in the invasion of tumor cells into the endothelial monolayer, which was found to be significant from 25 ng/ml, and peaked at levels of more than 50 ng/ml. This stimulatory effect of IL-6, which was observed from 3 h after the initiation of treatment and lasted for up to 24 h, was abolished by the addition of the anti-IL-6 antibody. Although phasecontrast microscopy did not reveal any morphological changes in the endothelial cells following treatment with 25–200 ng/ml IL-6 for 24h, the GJIC was observed to be significantly decreased. These findings indicate that the invasive capacity of tumor cells into endothelial cells is affected by IL-6.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Robinson KP, Hoppe E (1962) The development of blood-borne metastases. Archiv Surg 85:720–724.

    CAS  Google Scholar 

  2. Fisher ER, Fisher B (1965) Experimental study of factors influencing development of hepatic metastases from circulating tumor cells. Acta Cytol 9:146–159

    Google Scholar 

  3. Moore GE, Sandberg A, Schubarg JR (1957) Clinical and experimental observations of the occurrence and fate of tumor cells in the blood stream. Ann Surg 146:580–587

    CAS  PubMed  Google Scholar 

  4. Long L, Jonasson O, Roberts S, McGrath R, McGrew E, Cole WH (1960) Cancer cells in blood. Result of a simplified technique. Arch Surg 80:910–919

    CAS  PubMed  Google Scholar 

  5. Roberts S, Jonasson O, Long L, McGrew EA, McGrath R, Cole WH (1962) Relationship of cancer cells in the circulating blood to operation. Cancer 15:232–240

    CAS  PubMed  Google Scholar 

  6. Komada M, Komada T, Nishi Y, Totani R (1992) Does surgical stress cause tumor metastasis? Anticancer Res 12:1603–1616

    Google Scholar 

  7. Weiss L, Orr FW, Honn KV (1989) Interaction between cancer cells and the microvasculature: a rate regulator for metastasis. Clin Exp Metastasis 7:127–167

    CAS  PubMed  Google Scholar 

  8. Honn KV, Tang DG (1992) Adhesion molecules and tumor cell interaction with endothelial and subendothelia matrix. Cancer Metastasis Rev 11:353–375

    CAS  PubMed  Google Scholar 

  9. Paul BU, Augustin Voss HG, EI Sabban ME, Johnson RC, Hammer DA (1990) Organ preference of metastasis. The role of endothelial cell adhesion molecules. Cancer Metastasis Rev 9:175–189

    Google Scholar 

  10. Revel JP, Karnovsky MJ (1967) Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J Cell Biol 33:C7

    Article  CAS  PubMed  Google Scholar 

  11. Loewenstein WR (1979) Junctional intercellular communication and the control of growth. Biochim Biophys Acta 560:1–65

    CAS  PubMed  Google Scholar 

  12. Hertzberg EL, Laurence TS, Gilula NB (1981) Gap junctional communication. Annu Rev Physiol 43:479–491

    Article  CAS  PubMed  Google Scholar 

  13. Kishimoto K (1989) The biology of interleukin-6. Blood 74: 1–10

    CAS  PubMed  Google Scholar 

  14. Maruo N, Morita I, Shirao M, Murota S (1992) IL-6 increases endothelial permeability in vitro. Endocrinology 131:710–714

    Article  CAS  PubMed  Google Scholar 

  15. Nishimoto N, Yoshizaki K, Tagoh H (1989) Elevation of serum interleukin-6 prior to acute phase proteins on the inflammation by surgical operation. Clin Immunol Immunopathol 50:399–401

    Article  CAS  PubMed  Google Scholar 

  16. Ohzato H, Yoshizaki K, Nishimoto N (1992) Interleukin-6 as a new indicator of inflammatory status: Detection of serum levels of interleukin-6 and C-reactive protein after surgery. Surgery 111:201–209

    CAS  PubMed  Google Scholar 

  17. Ueo H, Inoue H, Honda M (1994) Production of interleukin-6 at operative wound site in surgical patients. J Am Coll Surg 179:326–332

    CAS  PubMed  Google Scholar 

  18. Sakamoto K, Arakawa H, Mita S (1994) Elevation of circulating interleukin-6 after surgery: Factors influencing the serum level. Cytokine 6:181–186

    Article  CAS  PubMed  Google Scholar 

  19. Mantovani A, Dejana E (1989) Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 10:370–375

    Article  CAS  PubMed  Google Scholar 

  20. Morita I, Kanayasu T, Murota S (1984) Kallikrein stimulates prostacyclin production in bovine vascular endothelial cells. Biochim Biophys Acta 792:304–309

    CAS  PubMed  Google Scholar 

  21. Voyta JC, Netland PA, Via DP, Zetter BR (1984) Specific labeling of endothelial cells using fluorescent acetylated-low density lipoprotein. J Cell Biol 99:81A

    Article  Google Scholar 

  22. Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T (1985) Purification to homogeneity and characterization of human B cell differentiation factor (BCDF or BSF-p2). Proc Natl Acad Sci USA 82:5490–5494

    CAS  PubMed  Google Scholar 

  23. Wade MH, Trosko JE, Schindler M (1986) A fluorescence photobleaching assay of gap junction-mediated communication between human cells. Science 232:525–528

    CAS  PubMed  Google Scholar 

  24. Baici A (1988) Tumor-host interaction in the rabbit V2 carcinoma; stimulation of cathepsin B in host fibroblasts by a tumorderived cytokine. Invasion Metastasis 8:143–158

    CAS  PubMed  Google Scholar 

  25. Weiss L, Orr FW, Honn KV (1988) Interaction of cancer cells with the microvasculature during metastasis. FASEB 2:12–21

    CAS  Google Scholar 

  26. Kramer RH, Nicolson GL (1979) Interaction of tumor cells with vascular endothelial cell monolayers: a model for metastatic invasion. Proc. Natl Acad Sci USA 76:5704–5708

    CAS  PubMed  Google Scholar 

  27. Lichtner RB, Belloni PN, Nicolson GL (1989) Differential adhesion of metastatic rat mammary carcinoma cells to organ-derived microvessel endothelial cells and endothelial matrix. Exp Cell Biol 57:146–152

    CAS  PubMed  Google Scholar 

  28. Strauri P, In-Albon A, Haemmerli G (1983) Morphological studies on V2 carcinoma invasion and tumor-associated connective tissue changes in the rabbit mesentery. Cancer Res 43:5403–5410

    Google Scholar 

  29. Armstrong PB, Quigley JP, Sidebottom E (1982) Transepithelial invasion and intramesenchymal infiltration of chick embryo chorioallantois by tumor cell lines. Cancer Res 42:1826–1837

    CAS  PubMed  Google Scholar 

  30. Ossowski L (1988) In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase. J Cell Biol 107:2437–2445

    Article  CAS  PubMed  Google Scholar 

  31. Liotta LA, Rao CN, Barsky SH (1983) Tumor invasion and the extracellular matrix. Lab Invest 49:636–649

    CAS  PubMed  Google Scholar 

  32. Yee C, Shiu RPC (1986) Degradation of endothelial basement membrane by human breast cancer cell lines. Cancer Res 46:1835–1839

    CAS  PubMed  Google Scholar 

  33. Cruicjshank AM, Fraster WD, Burnes HJ (1990) Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci 79:161–165

    Google Scholar 

  34. Murata A, Ogawa M, Yasuda T (1990) Serum interleukin-6, C-reactive protein and pancreatic secretory inhibitor (PSTI) as acute phase reactants after major thoraco-abdominal surgery. Immunol Invest 19:271–278

    CAS  PubMed  Google Scholar 

  35. Jones MO, Pierro A, Lloyd DA (1994) Postoperative changes in resting energy expenditure and interleukin-6 level in infants. Br J Surg 81:536–538

    CAS  PubMed  Google Scholar 

  36. Guo Y, Dickerson C, Chrest FJ (1990) Increased levels of circulating interleukin-6 in burn patients. Clin Immunol Immunopathol 54:361–371

    Article  CAS  PubMed  Google Scholar 

  37. Nijsten MWN, Hack CE, Helle M (1991) Interleukin-6 and its relation to the humoral immune response and clinical parameters in burned patients. Surgery 109:761–767

    CAS  PubMed  Google Scholar 

  38. Tsukamoto T, Kumamoto Y, Miyao N, Masumori N, Takahashi A, Yanase M (1992) Interleukin-6 in renal cell carcinoma. J Urol 148:1778–1782

    CAS  PubMed  Google Scholar 

  39. Otani N, Tsukamoto T, Saiki I, Yoneda J, Mitaka T, Kumamoto Y (1993) In vitro invasive potential and type IV collagenolytic activity of human renal carcinoma cells derived from primary and metastatic lesions. J Urol 149:1182–1185

    CAS  PubMed  Google Scholar 

  40. Takeda K, Fujii N, Nitta Y, Sakihara H, Nakayama K, Rikiishi H, Kumagai K (1991) Murine tumor cells metastasizing selectively in the liver: ability to produce hepatocyte-activating cytokines Interleukin-1 and/or-6. Jpn J Cancer Res 82:1299–1308

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kitamura, Y., Morita, I., Nihei, Z. et al. Effect of IL-6 on tumor cell invasion of vascular endothelial monolayers. Surg Today 27, 534–541 (1997). https://doi.org/10.1007/BF02385807

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02385807

Key Words

Navigation