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Effect of Herceptin on the development and progression of skeletal metastases in a xenograft model of human breast cancer

Oncogene volume 24, pages 6657–6666 (2005)Cite this article

A Corrigendum to this article was published on 19 January 2006

Abstract

We examined the effects of Herceptin, a bioengineered monoclonal antibody directed against Her-2/neu oncogene on skeletal metastasis using a xenograft model of breast cancer. Treatment of Her-2 overexpressing human breast cancer cells BT-474 with Herceptin caused a dose-dependent decrease in cell proliferation. In in vivo studies, BT-474 cells (1 × 105) were injected into the left ventricle of female BALB/c nu/nu mice. Intraperitoneal (i.p.) infusion of Herceptin (1 mg/kg twice a week for 5 weeks) from the day of tumor cell inoculation or at the time of radiologically detectable skeletal metastasis either slowed the development or prevented the progression of skeletal metastasis as compared to control groups of animals receiving nonspecific IgG. Bone histological analysis of long bones showed the ability of Herceptin to reduce the ratio of tumor volume to bone volume as well as mitotic index, effects that were more pronounced when Herceptin treatment was initiated from the day of tumor cell inoculation. While immunohistochemical analysis of long bones showed no difference in the production of Her-2, phosphorylated (P) Her-2 and MAPK, a significantly lower level of P-MAPK was seen in bones of Herceptin treated animals. These studies demonstrate the ability of Herceptin to inhibit the development and abrogate the progression of skeletal metastases associated with breast cancer by blocking the HER-2-mediated signaling pathways.

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Acknowledgements

We thank Dr Ida Khalili, Department of Radiology, McGill University Health Centre for carefully reviewing all X-rays. This work was supported by the Canadian Institutes of Health Research (CIHR) Grant MOP 10630 to SA Rabbani.

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Authors and Affiliations

  1. Department of Medicine and Oncology, McGill University Health Center, Montreal, H3A 1A1, QC, Canada

    Parisa Khalili, Ani Arakelian, Gaoping Chen & Shafaat A Rabbani

  2. Hamilton Regional Cancer Center, Hamilton, L8V 5C2, ON, Canada

    Gurmit Singh

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  1. Parisa Khalili
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  2. Ani Arakelian
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Correspondence to Shafaat A Rabbani.

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Khalili, P., Arakelian, A., Chen, G. et al. Effect of Herceptin on the development and progression of skeletal metastases in a xenograft model of human breast cancer. Oncogene 24, 6657–6666 (2005). https://doi.org/10.1038/sj.onc.1208790

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