Antitumor effect of recombinant human interleukin-2 on the growth of murine hemangioendothelioma D14 in nude mice: occurrence of large granular cells in the tumor

Jpn J Cancer Res. 1991 Aug;82(8):950-7. doi: 10.1111/j.1349-7006.1991.tb01926.x.

Abstract

The antitumor effect of recombinant human interleukin-2 (rIL-2) on murine hemangioendothelioma D14 (D14) in female BALB/c-nu/nu mice was examined histologically. D14 cells which had been maintained in vitro were transplanted subcutaneously into nude mice on day 0 (1 x 10(7) cells/mouse). The mice with established tumor on day 28 received rIL-2 subcutaneously at a dose of 20 micrograms/mouse/day for 35 days. On day 63, the mice were killed, and the tumor, spleen and bone marrow were examined histologically. In the mice that had received rIL-2, tumor growth was significantly suppressed. Histologically, there was marked infiltration of large granular cells (about 15-30 microns in diameter) in the tumors. In the adjacent areas, there was a significant increase in the number of tumor cells showing karyorrhexis. The large granular cells (LGC) contained periodic acid Schiff-positive round granules in the cytoplasm and were stained positively for Thy-1.2 surface antigen. The LGC were also positive for asialo GM1 surface antigen but not for Lyt-1, Lyt-2 or IgG surface antigens. This evidence suggests that the LGC are lymphokine-activated killer-like cells which were derived from a natural killer cell lineage. The concomitant increases in the number of LGC and the number of cells showing karyorrhexis in the tumors of the mice treated with rIL-2 suggest that LGC play an important role in the destruction of tumor cells.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow / pathology
  • Female
  • Hemangioendothelioma / immunology
  • Hemangioendothelioma / pathology
  • Hemangioendothelioma / therapy*
  • Immunohistochemistry
  • Interleukin-2 / therapeutic use*
  • Killer Cells, Lymphokine-Activated / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Recombinant Proteins / therapeutic use
  • Spleen / pathology

Substances

  • Antineoplastic Agents
  • Interleukin-2
  • Recombinant Proteins