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MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice
Tatsuo Kanda1, Amit Raychoudhuri, Robert Steele
1Department of Pathology, Saint Louis University, St. Louis, Missouri 63104, USA.
Abstract:
Breast cancer is the leading cause of cancer death among women. We have shown previously an antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of breast cancer growth and metastasis in an immunocompetent mouse model. For this, we have used a mouse breast cancer cell line (EO771) and syngeneic C57BL/6 mice. EO771 cells were implanted into the mammary fat pad of C57BL/6 mice. Replication-deficient recombinant adenovirus expressing MBP-1 was administered intratumorally to determine gene therapeutic potential. The results showed a significant regression of primary and distant (lung) tumor growth. Animals exhibited prolonged survival on treatment with MBP-1 compared with the control group (dl312). Subsequent studies suggested that MBP-1 inhibits matrix metalloproteinase expression in human breast cancer cells. Cells transduced with MBP-1 displayed inhibition of migration in a wound-healing assay. The conditioned medium from MBP-1-transduced cells blocked in vitro tube formation assay and inhibited expression of several angiogenic molecules. Taken together, our study shows that MBP-1 acts as a double-edged sword by inhibiting primary and metastatic tumor growth and modulating matrix metalloproteinase expression with a therapeutic potential against breast cancer progression.
Insights
MBP-1 gene therapy significantly reduced primary and distant breast cancer growth and prolonged survival in mice. This therapy also inhibited cancer cell migration and angiogenesis, showing potential for breast cancer treatment.
Area of Science:
- Oncology
- Gene Therapy
- Cancer Research
Background:
- Breast cancer remains a leading cause of cancer-related mortality in women.
- Previous research indicated MBP-1 exhibits antiproliferative effects on various human cancer cells.
Purpose of the Study:
- To evaluate MBP-1 as a gene therapeutic agent for inhibiting breast cancer growth and metastasis.
- To assess the efficacy of MBP-1 in an immunocompetent mouse model of breast cancer.
Main Methods:
- Utilized EO771 mouse breast cancer cells implanted in syngeneic C57BL/6 mice.
- Administered replication-deficient recombinant adenovirus expressing MBP-1 intratumorally.
- Assessed tumor regression, survival rates, cell migration, and angiogenesis markers.
Main Results:
- Significant regression of primary tumors and lung metastasis observed with MBP-1 treatment.
- Prolonged survival in mice treated with MBP-1 compared to control.
- MBP-1 inhibited matrix metalloproteinase expression, cell migration, and angiogenesis in vitro.
Conclusions:
- MBP-1 demonstrates therapeutic potential against breast cancer progression by inhibiting primary and metastatic tumor growth.
- MBP-1 acts as a 'double-edged sword' by targeting tumor growth and metastasis pathways.
- Gene therapy with MBP-1 warrants further investigation for breast cancer treatment.
