Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis

Sylvia Fong, Yoko Itahana, Tomoki Sumida, Jarnail Singh, Jean Philippe Coppe, Yong Liu, Peter C. Richards, James L. Bennington, Nancy M. Lee, Robert J. Debs, Pierre Yves Desprez

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187 Citations (Scopus)

Abstract

Mammary epithelial cells constitutively expressing Id-1 protein are unable to differentiate, acquire the ability to proliferate, and invade the extracellular matrix. In addition, Id-1 is aberrantly over-expressed in aggressive and metastatic breast cancer cells, as well as in human breast tumor biopsies from infiltrating carcinomas, suggesting Id-1 might be an important regulator of breast cancer progression. We show that human metastatic breast cancer cells become significantly less invasive in vitro and less metastatic in vivo when Id-1 is down-regulated by stable transduction with antisense Id-1. Expression of the matrix metalloproteinase MT1-MMP is decreased in proportion to the decrease in Id-1 protein levels, representing a potential mechanism for the reduction of invasiveness. Further, to more accurately recapitulate the biology of and potential therapeutic approaches to tumor metastasis, we targeted Id-1 expression systemically in tumor-bearing mice by using a nonviral approach. We demonstrate significant reduction of both Id-1 and MT1-MMP expressions as well as the metastatic spread of 4T1 breast cancer cells in syngeneic BALB/c mice. In conclusion, our studies have identified Id-1 as a critical regulator of breast cancer progression and suggest the feasibility of developing novel therapeutic approaches to target Id-1 expression to reduce breast cancer metastasis in humans.

Original languageEnglish
Pages (from-to)13543-13548
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number23
DOIs
Publication statusPublished - Nov 11 2003

All Science Journal Classification (ASJC) codes

  • General

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    Fong, S., Itahana, Y., Sumida, T., Singh, J., Coppe, J. P., Liu, Y., Richards, P. C., Bennington, J. L., Lee, N. M., Debs, R. J., & Desprez, P. Y. (2003). Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis. Proceedings of the National Academy of Sciences of the United States of America, 100(23), 13543-13548. https://doi.org/10.1073/pnas.2230238100