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Title 

Suppression of distant pulmonary metastasis of MDA-MB 435 human breast carcinoma established in mammary fat pads of nude mice by retroviral-mediated TIMP-2 gene transfer

Authors 

Y K LeeI S SoSang Chul LeeJeong-Hyung LeeChang Woo LeeHwan Mook KimM K ParkS T LeeD Y ParkD Y ShinC U ParkY S Kim

Publisher 

Wiley-Blackwell

Issue Date 

2005

Citation 

Journal of Gene Medicine, vol. 7, no. 2, pp. 145-157

Keywords 

breast cancerfat padpulmonary metastasisretroviral vectorTIMP-2tissue inhibitor of metalloproteinase 2angiogenesisbreast carcinomagene overexpressiongene transfer

Abstract 

Background: Previous studies have shown that TIMP-2 overexpression is a useful therapeutic tool for inhibiting tumor growth and invasion in animals. However, it has not been reported whether genetic manipulation for TIMP-2 overexpression can induce an inhibitory effect on s0pontaneous metastasis from the primary tumor site to other organs such as lungs or lymph nodes in an animal model. Methods: The present studies describe the effects of retrovirus-mediated TIMP-2 gene transfer into human breast cancer cell lines on the in vitro invasion of the tumor cells or the in vivo growth in nude mouse. Here we also used retroviral-mediated TIMP-2 overexpression by intratumoral injection for suppression of metastasis in human breast carcinoma established in the mammary fat pad of nude mice. Results: As expected, overexpression of TIMP-2 inhibited matrix metalloprotenase (MMP) activity and invasion of the tumor cells. Also, the growth rate of tumors grafted with the breast cancer cells transduced with the retrovirus vector encoding TIMP-2 cDNA was significantly slower than the growth rate of tumors grafted with the breast cancer cells transduced with a control retrovirus vector. Furthermore, single intratumoral injection of the TIMP-2 retrovirus-producing cells into human breast tumor tissue established in mammary fat pads of nude mice showed a dramatic decrease in size and number of lung metastatic tumors. Conclusions: Retrovirus-mediated TIMP-2 gene transfer into human breast cancer cells is able to down-regulate invasion and show that tumor-derived angiogenesis is reduced. In this model, retroviral-mediated transduction of TIMP-2 cDNA into a limited population of human tumor cells inhibits tumor growth and prevents distant pulmonary metastasis. These results indicate that it may not be necessary to deliver and express these genes in every single tumor cell as long as the level of expression in a limited number of transduced cells is sufficient to prevent the excessive breakdown of the extracellular matrix.

ISSN 

1099-498X

Link 

http://dx.doi.org/10.1002/jgm.645

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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