Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain

Diane Palmieri, Julie L. Bronder, Jeanne M. Herring, Toshiyuki Yoneda, Robert J. Weil, Andreas M. Stark, Raffael Kurek, Eleazar Vega-Valle, Lionel Feigenbaum, Douglas Halverson, Alexander Vortmeyer, Seth M. Steinberg, Kenneth Aldape, Patricia S. Steeg

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

Retrospective studies of breast cancer patients suggest that primary tumor Her-2 overexpression or trastuzumab therapy is associated with a devastating complication: the development of central nervous system (brain) metastases. Herein, we present Her-2 expression trends from resected human brain metastases and data from an experimental brain metastasis assay, both indicative of a functional contribution of Her-2 to brain metastatic colonization. Of 124 archival resected brain metastases from breast cancer patients, 36.2% overexpressed Her-2, indicating an enrichment in the frequency of tumor Her-2 overexpression at this metastatic site. Using quantitative real-time PCR of laser capture microdissected epithelial cells, Her-2 and epidermal growth factor receptor (EGFR) mRNA levels in a cohort of 12 frozen brain metastases were increased up to 5- and 9-fold, respectively, over those of Her-2-amplified primary tumors. Co-overexpression of Her-2 and EGFR was also observed in a subset of brain metastases. We then tested the hypothesis that overexpression of Her-2 increases the colonization of breast cancer cells in the brain in vivo. A subclone of MDA-MB-231 human breast carcinoma cells that selectively metastasizes to brain (231-BR) overexpressed EGFR; 231-BR cells were transfected with low (4- to 8-fold) or high (22- to 28-fold) levels of Her-2. In vivo, in a model of brain metastasis, low or high Her-2-overexpressing 231-BR clones produced comparable numbers of micrometastases in the brain as control transfectants; however, the Her-2 transfectants yielded 3-fold greater large metastases (>50 μm2; P < 0.001). Our data indicate that Her-2 overexpression increases the outgrowth of metastatic tumor cells in the brain in this model system.

Original languageEnglish (US)
Pages (from-to)4190-4198
Number of pages9
JournalCancer Research
Volume67
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

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Breast Neoplasms
Brain
Neoplasm Metastasis
Epidermal Growth Factor Receptor
Neoplasms
Neoplasm Micrometastasis
Real-Time Polymerase Chain Reaction
Lasers
Central Nervous System
Retrospective Studies
Clone Cells
Epithelial Cells
Messenger RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Palmieri, D., Bronder, J. L., Herring, J. M., Yoneda, T., Weil, R. J., Stark, A. M., ... Steeg, P. S. (2007). Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Research, 67(9), 4190-4198. https://doi.org/10.1158/0008-5472.CAN-06-3316

Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. / Palmieri, Diane; Bronder, Julie L.; Herring, Jeanne M.; Yoneda, Toshiyuki; Weil, Robert J.; Stark, Andreas M.; Kurek, Raffael; Vega-Valle, Eleazar; Feigenbaum, Lionel; Halverson, Douglas; Vortmeyer, Alexander; Steinberg, Seth M.; Aldape, Kenneth; Steeg, Patricia S.

In: Cancer Research, Vol. 67, No. 9, 01.05.2007, p. 4190-4198.

Research output: Contribution to journalArticle

Palmieri, D, Bronder, JL, Herring, JM, Yoneda, T, Weil, RJ, Stark, AM, Kurek, R, Vega-Valle, E, Feigenbaum, L, Halverson, D, Vortmeyer, A, Steinberg, SM, Aldape, K & Steeg, PS 2007, 'Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain', Cancer Research, vol. 67, no. 9, pp. 4190-4198. https://doi.org/10.1158/0008-5472.CAN-06-3316
Palmieri D, Bronder JL, Herring JM, Yoneda T, Weil RJ, Stark AM et al. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Research. 2007 May 1;67(9):4190-4198. https://doi.org/10.1158/0008-5472.CAN-06-3316
Palmieri, Diane ; Bronder, Julie L. ; Herring, Jeanne M. ; Yoneda, Toshiyuki ; Weil, Robert J. ; Stark, Andreas M. ; Kurek, Raffael ; Vega-Valle, Eleazar ; Feigenbaum, Lionel ; Halverson, Douglas ; Vortmeyer, Alexander ; Steinberg, Seth M. ; Aldape, Kenneth ; Steeg, Patricia S. / Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. In: Cancer Research. 2007 ; Vol. 67, No. 9. pp. 4190-4198.
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AU - Weil, Robert J.

AU - Stark, Andreas M.

AU - Kurek, Raffael

AU - Vega-Valle, Eleazar

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AU - Halverson, Douglas

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AU - Steeg, Patricia S.

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