Novel Monoclonal Antibody Blocks Breast Cancer Metastasis in Mouse Model

By LabMedica International staff writers
Posted on 01 Jul 2013

A monoclonal antibody specific for the protein ROR1 (Receptor-tyrosine-kinase-like Orphan Receptor 1) was found to inhibit cell migration and invasion in cancer cell cultures and block tumor metastasis in a mouse breast cancel model.

Investigators at the University of California, San Diego (USA) had shown previously that ROR1, which is expressed during embryonic development and by various cancers, was not active in normal postpartum tissues. In the current study, which was published in the June 15, 2013, issue of the journal Cancer Research, the investigators linked expression of ROR1 to the process of epithelial-mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis, and in the initiation of metastasis for cancer progression.

Image: Metastasized human breast cancer cells (magnified 400 times, stained brown) in lymph nodes (Photo courtesy of the [US] National Cancer Institute).

The investigators found that breast adenocarcinomas expressing high levels of ROR1 were more likely to have gene expression signatures associated with EMT and had higher rates of relapse and metastasis than breast adenocarcinomas expressing low levels of ROR1. Suppressing expression of ROR1 in metastasis-prone breast cancer cell lines attenuated expression of proteins associated with EMT and impaired their capacity for migration and invasion in vitro and for metastasis in immunodeficient mice.

Treatment of a mouse breast-cancer model with a monoclonal antibody specific for ROR1 induced down modulation of EMT-promoting proteins and inhibited cancer cell migration and invasion in vitro and tumor metastasis in vivo. The investigators concluded that this finding indicated that antibodies targeting ROR1 could inhibit cancer progression and metastasis.

“We might think of ROR1 as an oncogene,” said first author Dr. Bing Cui, a postdoctoral researcher at the University of California, San Diego. “This means ROR1 has some tumor initiation functions. However, ROR1 also appears to allow transformed cells to invade other tissues and to promote tumor expansion in both the primary tumor site and in distant organs.”

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University of California, San Diego