MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice.
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.
Kanda
Tatsuo
T
Department of Pathology, Saint Louis University, St. Louis, Missouri 63104, USA.
Raychoudhuri
Amit
A
Steele
Robert
R
Sagartz
John E
JE
West
Cheri
C
Ray
Ratna B
RB
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007121:Immunocompetence; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology
C088830:DENND4A protein, human; D004268:DNA-Binding Proteins; D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2