Metastatic behavior of the RIF-1 murine fibrosarcoma: inhibited by hypophysectomy and partially restored by growth hormone replacement.

Abstract

BACKGROUND:

We recently demonstrated that hypophysectomy profoundly inhibits metastatic behavior in the MGH-OGS murine osteosarcoma model and speculated that this effect is related at least in part to ablation of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis.

PURPOSE:

In this study, we determined whether the administration of GH to animals rendered GH and IGF-I deficient by hypophysectomy attenuates the inhibitory effects of hypophysectomy on metastatic behavior.

METHODS:

Metastatic behavior was assayed by counting visible metastases in lungs 3 weeks after tail vein injection of RIF-I fibrosarcoma cells to control mice (n = 29), hypophysectomized mice (n = 19), and hypophysectomized mice administered 0.05 microgram/g body weight recombinant human GH twice daily (n = 21).

RESULTS:

Twenty of 21 hypophysectomized mice receiving GH, eight of 19 hypophysectomized mice not receiving GH, and 26 of 29 controls had grossly visible pulmonary metastases 3 weeks after intravenous injection of 5 x 10(5) cells; mean numbers +/- SD of gross metastases were 38.4 +/- 11.3, 6.4 +/- 2.2, and 13.1 +/- 2.8 in the three groups, respectively. The presence (P < .005, chi-square test) and number (P = .0003, Mann-Whitney U test) of metastases were significantly reduced in hypophysectomized hosts compared with control hosts and were significantly higher in hypophysectomized, GH-replaced hosts compared with hypophysectomized hosts (P < .001, chi-square test; P = .011, Mann-Whitney U test), while the difference in presence and extent of metastases between control and hypophysectomized, GH-replaced hosts was not statistically significant.

CONCLUSIONS:

These data support the hypothesis that the status of the host with respect to GH and/or GH-dependent factors such as IGF-I influences the metastatic behavior of certain neoplasms.

IMPLICATIONS:

Our results raise the possibility that compounds that reduce GH output or interfere with GH action, such as somatostatin analogues, GH antagonists, IGF antagonists, and GH-releasing hormone antagonists, may suppress metastatic behavior of certain neoplasms.

• Authors: A Sekyi-Otu, R Bell, I Andrulis, M Pollak
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 86 Issue 8 Pg. 628-32 (Apr 20 1994) ISSN: 0027-8874 [Print] United States
• PMID: 8145278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor I
• Growth Hormone

Topics

• Animals
• Fibrosarcoma (prevention & control, secondary)
• Growth Hormone (physiology)
• Hypophysectomy
• Insulin-Like Growth Factor I (physiology)
• Male
• Mice
• Mice, Inbred C3H
• Tumor Cells, Cultured