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

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
박미경Young-Kwan LeeIn-Seob SoSang-Chul LeeJeong-Hyung LeeChang-Woo LeeWhan-Mook KimSeung-Taik LeeDo-Youn ParkDeug-Yong ShinChung-Ung ParkYeon-Soo Kim
Issue Date
2005-02
Publisher
The journal of gene medicine
Citation
VOL 7-157
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 spontaneous 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 c
URI
http://pubs.kist.re.kr/handle/201004/71073
ISSN
1099-498X
Appears in Collections:
KIST Publication > Article
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