Related Experiment Video
Updated: Jun 23, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Clinical-translational strategies for the elevation of Nm23-H1 metastasis suppressor gene expression
Jean-Claude Marshall1, Jong Heun Lee, Patricia S Steeg
1Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. marshallje@mail.nih.gov
Abstract:
Interruption of the tumor metastatic process is a new, thought provoking molecular target for the treatment of cancer. The Nm23-H1 metastasis suppressor gene stands as a validated molecular target owing to its reduced expression in many aggressive human tumors, and the reduction in metastatic potential in vivo upon re-expression in multiple cell lines. Several compounds have been identified which elevate Nm23-H1 expression in vitro including indomethacin, gamma Linolenic Acid, trichostatin A, 5-aza-deoxycytidine, and high dose medroxyprogesterone acetate. Using a model of lung metastatic colonization by MDA-MB-231 human breast carcinoma cells, we demonstrated that high dose MPA reduced the formation of overt lung metastases by 37-46% and those metastases that formed were statistically smaller. A Phase II clinical trial of high dose MPA, alone or in combination with metronomic chemotherapy has recently opened.
Insights
High-dose medroxyprogesterone acetate (MPA) effectively suppresses breast cancer metastasis by targeting the Nm23-H1 gene. This finding supports MPA as a potential therapeutic agent for reducing metastatic spread in cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The Nm23-H1 metastasis suppressor gene is a validated molecular target for cancer treatment due to its decreased expression in aggressive tumors.
- Re-expression of Nm23-H1 has been shown to reduce metastatic potential in various cancer cell lines.
Purpose of the Study:
- To investigate the efficacy of compounds that elevate Nm23-H1 expression, specifically high-dose medroxyprogesterone acetate (MPA).
- To evaluate the impact of high-dose MPA on lung metastatic colonization in a human breast carcinoma model.
Main Methods:
- Utilized a xenograft model involving MDA-MB-231 human breast carcinoma cells to study lung metastatic colonization.
- Administered high-dose medroxyprogesterone acetate (MPA) and assessed its effect on metastasis formation and size.
Main Results:
- High-dose MPA demonstrated a significant reduction in overt lung metastases, ranging from 37% to 46%.
- Metastases that did form in MPA-treated groups were statistically smaller compared to controls.
- Identified several compounds, including indomethacin and gamma Linolenic Acid, that can increase Nm23-H1 expression in vitro.
Conclusions:
- High-dose MPA effectively reduces the formation and size of lung metastases in a preclinical breast cancer model.
- Nm23-H1 gene expression modulation represents a promising strategy for inhibiting cancer metastasis.
- A Phase II clinical trial investigating high-dose MPA for cancer treatment is currently underway.
