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Determinants of differential liver-colonizing potential of variants of the MCA-38 murine colon cancer cell line

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We investigated factors that might contribute to the differing liver tumor colonizing potentials of MCA-38 colonic cancer cell line variants injected into the ileocolic veins of C57B1/6J mice. Non-colonizing (MCA-38 CD) cells were sensitive to lysis by hepatic ntural killer (NK) cells in vitro (51 Cr-release assay) and cells with high liver-colonizing potential (MCA-38 LD) were resistant. Following abrogation of NK activity by treatment with anti-asialoGM1, liver-colonizing ability of LD cells but not CD cells was enhanced. MCA-38 CD cells were, however, capable of initial liver colonization after ileocolic vein injection. Differing patterns of membrane sialylation may have contributed to the contrasting hepatic tumorigenicities of LD and CD cells; β-galactoside α2,6-sialyltransferase mRNA levels and activity were ∼ four-fold higher in LD than CD cells and qualitative and quantitative differences existed between their ganglioside profiles. In the MCA-38 model outlined, tumor cell susceptibility or resistance to NK lysis was a relatively unimportant determinant of liver-colonizing potential.

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References

  1. Tan MH, Holyoke ED and Goldrosen MH, 1977, Murine colon adenocarcinoma: syngeneic orthotopic transplantation and subsequent hepatic metastases. J Natl Cancer Inst, 59, 1537–44.

    Google Scholar 

  2. Goldrosen MH, 1980, Murine colon adenocarcinoma: immunobiology of metastases. Cancer, 45, 1223–8.

    Google Scholar 

  3. Goldrosen MH, Paolini Jr N and Holyoke ED, 1986, Description of a murine model of experimental hepatic metastases. J Natl Cancer Inst, 77, 823–8.

    Google Scholar 

  4. Tzung S-P and Cohen SA, 1992, Antitumor defense system of the liver. In: Billiar TR, Curran RD, eds. Kupffer Cells and Hepatocyte Interactions. Boca Raton: CRC Press, pp. 73–95.

    Google Scholar 

  5. Roh MS, Kahky MP, Oyedeji C, et al. 1992, Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases. Clin Exp Metastasis, 10, 317–27.

    Google Scholar 

  6. Hanna N and Fidler IJ, 1980, Role of natural killer cells in the destruction of circulating tumor enboli. J Natl Cancer Inst, 65, 801–12.

    Google Scholar 

  7. Markovic SN and Murasko DM, 1990, Neoadjuvant immunotherapy with interferon of the spontaneously metastasizing murine B16F10L melanoma. Int J Cancer, 45, 788–94.

    Google Scholar 

  8. Markovic SN and Murasko DM, 1991, Role of natural killer and T-cells in interferon induced inhibition of spontaneous metastases of the B16F10L murine melanoma. Cancer Res, 51, 1124–8.

    Google Scholar 

  9. Cohen A, Tzung S-P, Doerr RJ and Goldrosen MH, 1990, Role of asialo-GM1 liver cells from athymic nude or polyinosinic-polycytidylic acid-treated mice in suppressing colon-derived experimental hepatic metastasis. Cancer Res, 50, 1834–40.

    Google Scholar 

  10. Arisawa A, Kubota T, Kodaira S, Ishibiki K and Abe O, 1990, Nude mouse resists hepatic metastasis of the allogenic tumor, colon-26. Jpn J Surg, 20, 487–90.

    Google Scholar 

  11. Werner-Wasik M, von Meunchhausen W, Nolan JP and Cohen SA, 1989, Endogenous interferon ga/β produced by murine Kupffer cells augments liver associated natural killer activity. Cancer Immunol Immunother, 35, 103–12.

    Google Scholar 

  12. Maslow DE and Goldrosen MH, 1988, Relationship of in vitro cell motility and colonization potential in a mouse colon adenocarcinoma (MCA-38) cell line. Inv Metastasis, 8, 133–42.

    Google Scholar 

  13. Chirgwin JM, Przybyla AE, MacDonald RJ and Rutter WJ, 1979, Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18, 5294–9.

    Google Scholar 

  14. Shah S, Lance P, Smith TJ, et al. 1992, n-Butyrate reduces the expression of β-galactoside α2,6-sialyltransferase in Hep G2 cells. J Biol Chem, 267, 10652–8.

    Google Scholar 

  15. Feinberg AP and Vogelstein B, 1983, A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem, 132, 6–13.

    Google Scholar 

  16. Lance P, Lau KM and Lau JTY, 1989, Isolation and characterization of a partial cDNA for a human sialyltransferase. Biochem Biophys Res Commun, 164, 225–32.

    Google Scholar 

  17. Brenen M and Parish CR, 1984, Intracellular labelling of cells for analysis of lymphocyte migration. J Immunol Meth, 74, 31–8.

    Google Scholar 

  18. Brenan M, Parish CR and Schoefl GI, 1985, Topographical studies of lymphocyte localization using an intracellular fluorochrome. Anat Rec, 213, 421–8.

    Google Scholar 

  19. Wang X, O'Hanlon TP and Lau JTY, 1989, Regulation of β-galactoside α2,6-sialyltransferase gene expression by dexamethasone. J Biol Chem, 264, 1854–9.

    Google Scholar 

  20. Baxter A and Durham JP, 1979, A rapid, sensitive disk assay for the determination of glycoprotein glycosyl-transferases. Anal Biochem, 98, 95–101.

    Google Scholar 

  21. Kaplan HA, Woloski BMRNJ, Hellman M and Jamieson JC, 1983, Studies on the effect of inflammation on rat liver and serum sialyltransferase. J Biol Chem, 258, 11505–9.

    Google Scholar 

  22. Bradford M, 1976, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the pronciple of protein-dye binding. Anal Biochem, 72, 248–54.

    Google Scholar 

  23. Kaneda K, 1989, Liver-associated large granular lymphocytes: morphological and functional aspects. Arch Histol Cytol, 52, 447–59.

    Google Scholar 

  24. Cohen SA, Salazar D and Nolan JP, 1982, Natural cytotoxicity of isolated rat liver cells. J Immunol, 129, 495–501.

    Google Scholar 

  25. Tzung S-P, Gaines KC, Lance P, Ehrke J and Cohen SA, 1990, Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes. Hepatology, 12, 644–52.

    Google Scholar 

  26. Tan MH, 1979, Pathogenesis of metastasis in colorectal and cutaneous tumors: studies in two syngeneic murine model systems (Ph.D. Dissertation). State University of New York at Buffalo.

    Google Scholar 

  27. Bresalier RS, Rockwell RW, Dahiya R, Duh Q and Kim YS, 1990, Cell surface sialoprotein alterations in metastatic murine colon cancer cell lines selected in an animal model for colon cancer metastasis. Cancer Res, 50, 1299–307.

    Google Scholar 

  28. Kijima-Suda I, Miyamoto Y, Toyoshima S, Itoh M and Osawa T, 1986, Inhibition off experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid: nucleoside conjugate having sialyl-transferase inhibiting activity. Cancer Res, 46, 858–62.

    Google Scholar 

  29. Kasai M, Yoneka T, Habu S, et al. 1981, In vivo effect of anti-asialo GM1 antibody on natural killer activity. Nature, 291, 334–6.

    Google Scholar 

  30. Trinchieri G, 1989, Biology of natural killer cells. Adv Immunol, 47, 187–376.

    Google Scholar 

  31. Shiratori Y, Nakata R, Okano K, et al. 1992, Inhibition of hepatic metastasis of colon carcinoma by asialo GM1-positive cells in the liver. Hepatology, 16, 469–78.

    Google Scholar 

  32. Johnkoski JA, Hseuh C, Doerr RJ and Cohen SA, 1992, Levamisole augments the immune response of the murine liver. Am J Surg, 163, 202–7.

    Google Scholar 

  33. Xu ZL, Bucana CD and Fidler IJ, 1984, In vivo activation of murine Kupffer cells by lymphokines or endotoxins to lyse syngeneic tumor cells. Am J Pathol, 117, 372–9.

    Google Scholar 

  34. Dall'Olio F, Malagolini N, Di Stefano G, et al. 1989, Increased CMP-NeuAc:Galβ1,4GlcNac-R α2,6 sialyltransferase activity in human colorectal cancer tissues. Int J Cancer, 44, 434–9.

    Google Scholar 

  35. Kemmner W, Kruck D and Schlag P, 1994, Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors. Clin Exp Metastasis, 12, 245–54.

    Google Scholar 

  36. Mostafapour MK and Goldstein IJ, 1993, Cultured Ehrlich ascites tumor cells show increased N-linked α2,6-sialyltransferase activity. Arch Biochem Biophys, 303, 255–9.

    Google Scholar 

  37. Holmes EH and Hakomori S, 1983, Enzymatic basis for changes in fucoganglioside during chemical carcinogenesis. J Biol Chem, 258, 3706–13.

    Google Scholar 

  38. Fukushi Y, Nudelman E, Levery SB, Hakomori S and Rauvala H, 1984, Novel fucolipids accumulating in human adenocarcinoma. J Biol Chem, 259, 10511–7.

    Google Scholar 

  39. Kitagawa H, Nakada H, Fukui S, et al. 1993, Novel gangliosides containing the sialyl-Lea structure from a human rectal adenocarcinoma. J Biol Chem 268, 26541–5.

    Google Scholar 

  40. Miyake M and Hakomori S, 1991, A specific cell surface glycoconjugate controlling cell motility: evidence by functional monoclonal antibodies that inhibit cell motility and tumor cell metastasis. Biochemistry, 30, 3328–34.

    Google Scholar 

  41. Coulombe J and Pelletier G, 1993, Gangliosides and organ-specific metastatic colonization. Int J Cancer, 53, 104–9.

    Google Scholar 

  42. Bremer EG, Hakomori S, Bowen-Pope DF, Raines E and Ross R, 1984, Ganglioside-mediated modulation of cell growth, growth factor binding, and receptor phosphorylation. J Biol Chem, 259, 6818–25.

    Google Scholar 

  43. Hanai N, Dohi T, Nores GA and Hakomori S, 1988, A novel ganglioside, De-N-acetyl-GM3 (II3NeuNH2LacCer), acting as a strong promoter for epidermal growth factor receptor kinase and as a stimulator for cell growth. J Biol Chem, 263, 6296–301.

    Google Scholar 

  44. Hersey P, MacDonald M, Burns C and Cheresh DA, 1987, Enhancement of cytotoxic and proliferative responses of lymphocytes from melanoma patients by incubation with monoclonal antibodies against ganglioside GD3. Cancer Immunol Immunother, 24, 144–50.

    Google Scholar 

  45. Ladisch S, Gillard B, Wong C and Ulsh L, 1983, Shedding and immunoregulatory activity of YAC-1 lymphoma cell gangliosides. Cancer Res, 43, 3808–13.

    Google Scholar 

  46. Hoon DSB, Irie RF and Cochran AJ, 1988, Gangliosides from human melanoma immunomodulate response of T cells to interleukin-2. Cell Immunol, 111, 410–19.

    Google Scholar 

  47. Valentino L, Moss T, Olson E, et al. 1990, Shed tumor gangliosides and progression of human neuroblastoma. Blood, 75, 1564–7.

    Google Scholar 

  48. Gonwa TA, Westrick MA and Macher BA, 1984, Inhibition of mitogen- and antigen-induced lymphocyte activation by human leukemia cell gangliosides. Cancer Res, 44, 3467–70.

    Google Scholar 

  49. Voshol H, Dullens HFJ, Den Otter W and Vliegenthart FG, 1993, Cell surface glycoconjugates as possible target structures for human natural killer cells: evidence against the involvement of glycolipids and N-linked carbohydrate chains. Glycobiology, 3, 69–76.

    Google Scholar 

  50. McCoy JP Jr and Chambers WH, 1991, Carbohydrates in the functions of natural killer cells. Glycobiology, 1, 321–8.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, State University of New York at Buffalo, USA

    James J. Piscatelli, Stephan A. Cohen & Peter Lance

  2. Department of Gastroenterology, VA Medical Center, Buffalo, New York, USA

    Charles S. Berensont

  3. Infectious Diseases Sections, VA Medical Center, Buffalo, New York, USA

    Charles S. Berensont

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  1. James J. Piscatelli
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  2. Stephan A. Cohen
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  3. Charles S. Berensont
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  4. Peter Lance
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Piscatelli, J.J., Cohen, S.A., Berensont, C.S. et al. Determinants of differential liver-colonizing potential of variants of the MCA-38 murine colon cancer cell line. Clin Exp Metast 13, 141–150 (1995). https://doi.org/10.1007/BF00133619

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