Inhibition of breast tumor progression by systemic delivery of the maspin gene in a syngeneic tumor model.
Maspin has been shown to possess tumor-suppressing activity against breast tumor growth and metastasis. To test the therapeutic value of the maspin gene (SERPINB5) in breast cancer, we established a syngeneic breast tumor metastasis model. This model involved the implantation of mammary tumor cells orthotopically to mammary gland and allowed tumors to grow within the gland and become metastatic to other organs. The mammary tumor cells were initially isolated from MMTV-polyoma virus middle T transgenic mice and were selected in vitro for high invasiveness. Here, we demonstrate that the mammary tumor cells were highly invasive and metastatic. Overall, 100% of tumor-transplanted mice developed lung metastasis. Using nonviral liposome as a carrier, we delivered SERPINB5 to mice bearing mammary tumors. Our data showed that both primary tumor growth and metastasis were significantly inhibited in this syngeneic metastasis model. Such inhibition is mediated by SERPINB5 transgene through increased apoptosis in SERPINB5-treated tumors. Thus, SERPINB5 can be used in gene therapy against breast tumor growth and metastasis.
Shi
Heidi Y
HY
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Liang
Rong
R
Templeton
Nancy S
NS
Zhang
Ming
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000556:secondary / Q000628:therapy*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics / Q000627:therapeutic use*; D015843:Serpins / Q000235:genetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins; D015500:Chloramphenicol O-Acetyltransferase