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. 1987 Apr;24(2):93–98. doi: 10.1007/BF00205584

Recruitment of exogenous macrophages into metastases at different stages of tumor growth

Peter J Bugelski 1,, Richard Kirsh 2, Charles Buscarino 3, Steven P Corwin 3, George Poste 3,5
PMCID: PMC11038418  PMID: 3829054

Abstract

The endogenous tumor-associated macrophage content and recruitment of labeled peritoneal exudate cells into experimental murine B16 melanoma metastases has been examined at different stages in the progressive growth of metastatic lesions. The recruitment of thioglycollate-elicited peritoneal exudate cells and peritoneal exudate cells activated in vitro with muramyl dipeptide was studied. Tumor-associated macrophages and labeled peritoneal exudate cells were identified in paraffin sections by specific histochemical staining and their density in individual metastases measured morphometrically. The density of tumor-associated macrophages and exogenously recruited peritoneal exudate cells was high in very small lesions but decreased rapidly as a function of enlargement of metastases, MD:An; where MD is macrophage density, A is the cross-sectional area of the lesion and n is a negative number. No significant difference was observed in the recruitment of activated and nonactivated peritoneal exudate cells. These results suggest that decreased recrutiment of macrophages from the circulation may explain the decrease in the density of tumor-associated macrophages as metastases grow and indicate that macrophage activation is not accompanied by enhanced localization and/or uptake of macrophages into metastases.

Keywords: Melanoma, Paraffin, Dipeptide, Metastatic Lesion, Paraffin Section

References

  • 1.Adams DO, Hamilton TA. The cell biology of macrophage activation. Ann Rev Immunol. 1984;2:283. doi: 10.1146/annurev.iy.02.040184.001435. [DOI] [PubMed] [Google Scholar]
  • 2.Blusse' van Oud Alblas A, Mattie H, van Furth R. A quantitative evaluation of pulmonary macrophage kinetics. Cell Tissue Kinet. 1983;16:211. [PubMed] [Google Scholar]
  • 3.Bugelski PJ, Kirsh RL, Poste G. New histochemical method for measuring intratumoral macrophages and macrophage recruitment into experimental metastases. Cancer Res. 1983;43:5493. [PubMed] [Google Scholar]
  • 4.Bugelski PJ, Kirsh RL, Sowinski JM, Poste G. Changes in the macrophage content of lung metastases at different stages in tumor growth. Am J Pathol. 1985;118:419. [PMC free article] [PubMed] [Google Scholar]
  • 5.Deodhar SD, James K, Chiang T, Edinger M, Barna BP. Inhibition of lung metastases in mice bearing a malignant fibrosarcoma by treatment with liposomes containing human C-reactive protein. Cancer Res. 1982;42:5084. [PubMed] [Google Scholar]
  • 6.Ettinghausen SE, Rosenberg SA. The adoptive immunotherapy of cancer using lymphokine activated killer cells and recombinant Interleukin-2. Springer Semin Immunopathol. 1986;9:51. [PubMed] [Google Scholar]
  • 7.Fey F, Arnold W, Graffi A. Demonstration of the stimulation of the reticulohistiocytic system (RHS) of mice by treatment with BCG by means of biometric and histochemical techniques. Eur J Cancer. 1976;12:595. doi: 10.1016/0014-2964(76)90183-3. [DOI] [PubMed] [Google Scholar]
  • 8.Fidler IJ. Inhibition of pulmonary metastases by intravenous injection of specifically activated macrophages. Cancer Res. 1974;34:1074. [PubMed] [Google Scholar]
  • 9.Fidler IJ. Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines. Science. 1981;208:1469. doi: 10.1126/science.7384789. [DOI] [PubMed] [Google Scholar]
  • 10.Fidler IJ, Poste G. Macrophage-mediated destruction of malignant tumor cells and new strategies for the therapy of metastatic disease. Springer Semin Immunopathol. 1982;5:161. doi: 10.1007/BF00199794. [DOI] [PubMed] [Google Scholar]
  • 11.Fidler IJ, Barnes Z, Fogler WE, Kirsh R, Bugelski P, Poste G. Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators. Cancer Res. 1982;42:496. [PubMed] [Google Scholar]
  • 12.Gorelik E, Wiltrout RH, Copeland D, Herberman RB. Modulation of formation of tumor metastases by peritoneal macrophages elicited by various agents. Cancer Immunol Immunother. 1985;19:35. doi: 10.1007/BF00199309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Hibbs JB. Discrimination between neoplastic and nonneoplastic cells in vitro by activated macrophages. J Natl Cancer Inst. 1974;53:1487. doi: 10.1093/jnci/53.5.1487. [DOI] [PubMed] [Google Scholar]
  • 14.Kalish R, Brody NI. The effects of tumor facilitating factor of B16 melanoma on the macrophage. J Invest Dermatol. 1983;80:162. doi: 10.1111/1523-1747.ep12533308. [DOI] [PubMed] [Google Scholar]
  • 15.Keller R, Jones V. Role of activated macrophages and antibody in inhibition and enhancement of tumor growth in rats. Lancet. 1971;II:847. doi: 10.1016/s0140-6736(71)90222-4. [DOI] [PubMed] [Google Scholar]
  • 16.Nash JRG. Macrophages in human tumors: An immunohistochemical study. J Pathol. 1982;136:73. doi: 10.1002/path.1711360202. [DOI] [PubMed] [Google Scholar]
  • 17.Normann SJ, Cornelius J. Concurrent depression of tumor macrophage infiltration and systemic inflammation by progressive cancer growth. Cancer Res. 1978;38:3453. [PubMed] [Google Scholar]
  • 18.Roser B. The distribution of intravenously injected peritoneal macrophages in the mouse. Aust J Exp Biol Med Sci. 1965;43:553. doi: 10.1038/icb.1965.41. [DOI] [PubMed] [Google Scholar]
  • 19.Sone S, Fidler IJ. In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. Cell Immunol. 1981;57:42. doi: 10.1016/0008-8749(81)90118-0. [DOI] [PubMed] [Google Scholar]
  • 20.Wood GW, Gallahon KA. Detection and quantitation of macrophage infiltration into primary human tumors with the use of cell surface markers. J Natl Cancer Inst. 1977;59:1081. doi: 10.1093/jnci/59.4.1081. [DOI] [PubMed] [Google Scholar]

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