Recombinant human prolactin improves antitumor effects of murine natural killer cells in vitro and in vivo

Rui Sun, Haiming Wei, Jianhua Zhang, Ailing Li, Weici Zhang, Zhi Gang Tian

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Objective: To verify the effect of prolactin on natural killer (NK) cells in vivo and its implications for NK cell immunotherapy. Methods: Recombinant human prolactin (rhPRL; 30 μg, i.p.) was administered to BALB/c mice and severe combined immunodeficiency (SCID) mice 1 day before harvesting splenocytes for 51Cr release assay to examine the effects of rhPRL on NK cells of normal mice. rhPRL (10 μg, i.p., every other day for a total of 5 injections) was administered to BALB/c mice after syngeneic bone marrow transplantation (SBMT) to determine its effects on NK cell reconstitution. CT26 tumor cells were injected into BALB/c mice intravenously on day 0, and interleukin (IL)-15-cocultured activated syngeneic NK cells (IL-15-NK) from SCID mice were intravenously injected into tumor-bearing BALB/c mice on day 1. The improvement of antimetastasis effects and survival of tumor-bearing mice by rhPRL were checked. Results: BALB/c and SCID mice receiving one rhPRL injection exhibited a significant increase in cellular cytotoxicity against YAC-1 target tumor cells; the specific lysis was enhanced from 12.5 to 17.3% in BALB/c mice and from 27.8 to 51.2% in SCID mice. BALB/c mice continuously receiving rhPRL injections exhibited significant increases in NK cell (DX5-positive) contents and cellularity in both the bone marrow and spleen in the SBMT model. The bone marrow NK cell contents were improved from 1.53 to 3.13% after rhPRL injection. NK cells from SCID mice were then cultured with recombinant human IL-15 (rhIL-15; 6,000 IU/ml), rhPRL (10 ng/ml) or rhIL-15 plus rhPRL for 25 days. The cytotoxicity and cellularity were enhanced by rhPRL when tested on day 10, when comparing the rhIL-15 plus rhPRL group with the rhIL-15 group or rhPRL group, respectively. In the adoptive cellular immunotherapy study, the IL-15-NK plus IL-15 plus rhPRL group showed significantly lower numbers of lung metastases and longer survival than the IL-15-NK plus IL-15 group; the mean survival interval was prolonged from 31.5 to 53.7 days. Conclusion: These results indicate that rhPRL is possibly an important regulator of NK cells and a potential biologic product for immunotherapy. Copyright

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalNeuroImmunoModulation
Volume10
Issue number3
DOIs
StatePublished - Dec 1 2002
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Natural killer cell
  • Prolactin
  • Tumor metastasis

ASJC Scopus subject areas

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems

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