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

Young Kwan Lee, In Seob So, Sang Chul Lee, Jeong Hyung Lee, Chang Woo Lee, Whan Mook Kim, Mi Kyung Park, Seung Taik Lee, Do Youn Park, Deug Yong Shin, Chung Ung Park, Yeon Soo Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)145-157
Number of pages13
JournalJournal of Gene Medicine
Volume7
Issue number2
DOIs
Publication statusPublished - 2005 Feb 1

Fingerprint

Tissue Inhibitor of Metalloproteinase-2
Nude Mice
Adipose Tissue
Breast
Breast Neoplasms
Neoplasm Metastasis
Lung
Retroviridae
Genes
Neoplasms
Growth
Complementary DNA
Injections
Extracellular Matrix
Down-Regulation
Animal Models
Cell Count
Lymph Nodes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

Cite this

Lee, Young Kwan ; So, In Seob ; Lee, Sang Chul ; Lee, Jeong Hyung ; Lee, Chang Woo ; Kim, Whan Mook ; Park, Mi Kyung ; Lee, Seung Taik ; Park, Do Youn ; Shin, Deug Yong ; Park, Chung Ung ; Kim, Yeon Soo. / 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. In: Journal of Gene Medicine. 2005 ; Vol. 7, No. 2. pp. 145-157.
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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",
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.",
author = "Lee, {Young Kwan} and So, {In Seob} and Lee, {Sang Chul} and Lee, {Jeong Hyung} and Lee, {Chang Woo} and Kim, {Whan Mook} and Park, {Mi Kyung} and Lee, {Seung Taik} and Park, {Do Youn} and Shin, {Deug Yong} and Park, {Chung Ung} and Kim, {Yeon Soo}",
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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. / Lee, Young Kwan; So, In Seob; Lee, Sang Chul; Lee, Jeong Hyung; Lee, Chang Woo; Kim, Whan Mook; Park, Mi Kyung; Lee, Seung Taik; Park, Do Youn; Shin, Deug Yong; Park, Chung Ung; Kim, Yeon Soo.

In: Journal of Gene Medicine, Vol. 7, No. 2, 01.02.2005, p. 145-157.

Research output: Contribution to journalArticle

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T1 - 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

AU - Lee, Young Kwan

AU - So, In Seob

AU - Lee, Sang Chul

AU - Lee, Jeong Hyung

AU - Lee, Chang Woo

AU - Kim, Whan Mook

AU - Park, Mi Kyung

AU - Lee, Seung Taik

AU - Park, Do Youn

AU - Shin, Deug Yong

AU - Park, Chung Ung

AU - Kim, Yeon Soo

PY - 2005/2/1

Y1 - 2005/2/1

N2 - 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.

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