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.
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References
Robinson KP, Hoppe E (1962) The development of blood-borne metastases. Archiv Surg 85:720–724.
Fisher ER, Fisher B (1965) Experimental study of factors influencing development of hepatic metastases from circulating tumor cells. Acta Cytol 9:146–159
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
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
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
Komada M, Komada T, Nishi Y, Totani R (1992) Does surgical stress cause tumor metastasis? Anticancer Res 12:1603–1616
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
Honn KV, Tang DG (1992) Adhesion molecules and tumor cell interaction with endothelial and subendothelia matrix. Cancer Metastasis Rev 11:353–375
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
Revel JP, Karnovsky MJ (1967) Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J Cell Biol 33:C7
Loewenstein WR (1979) Junctional intercellular communication and the control of growth. Biochim Biophys Acta 560:1–65
Hertzberg EL, Laurence TS, Gilula NB (1981) Gap junctional communication. Annu Rev Physiol 43:479–491
Kishimoto K (1989) The biology of interleukin-6. Blood 74: 1–10
Maruo N, Morita I, Shirao M, Murota S (1992) IL-6 increases endothelial permeability in vitro. Endocrinology 131:710–714
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
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
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
Sakamoto K, Arakawa H, Mita S (1994) Elevation of circulating interleukin-6 after surgery: Factors influencing the serum level. Cytokine 6:181–186
Mantovani A, Dejana E (1989) Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 10:370–375
Morita I, Kanayasu T, Murota S (1984) Kallikrein stimulates prostacyclin production in bovine vascular endothelial cells. Biochim Biophys Acta 792:304–309
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
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
Wade MH, Trosko JE, Schindler M (1986) A fluorescence photobleaching assay of gap junction-mediated communication between human cells. Science 232:525–528
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
Weiss L, Orr FW, Honn KV (1988) Interaction of cancer cells with the microvasculature during metastasis. FASEB 2:12–21
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
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
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
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
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
Liotta LA, Rao CN, Barsky SH (1983) Tumor invasion and the extracellular matrix. Lab Invest 49:636–649
Yee C, Shiu RPC (1986) Degradation of endothelial basement membrane by human breast cancer cell lines. Cancer Res 46:1835–1839
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
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
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
Guo Y, Dickerson C, Chrest FJ (1990) Increased levels of circulating interleukin-6 in burn patients. Clin Immunol Immunopathol 54:361–371
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
Tsukamoto T, Kumamoto Y, Miyao N, Masumori N, Takahashi A, Yanase M (1992) Interleukin-6 in renal cell carcinoma. J Urol 148:1778–1782
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
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
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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
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DOI: https://doi.org/10.1007/BF02385807