Protein that Determines Spread of Breast Cancer

Researchers have found that lysyl-oxidase-related protein (LOR-1) acts by promoting cell migration and stimulating collagen synthesis to enable breast cancer cells to metastasize.

Investigators at the Technion Institute of Technology (Haifa, Israel) cultured lines of breast cancer cells that lacked the LOR-1 gene and compared them to breast cancer cells that had been genetically engineered to produce LOR-1. The two types of cells were injected into mice to produce cancer tumors. They found that only the cells that produced LOR-1 became invasive and acquired the characteristics of highly malignant and metastatic cancer cells, such as an ability to migrate into blood vessels. In contrast, cells that did not make LOR-1 produced benign, non-invasive tumors. These findings were published in the April 1, 2003, issue of Cancer Research.

Similarly, only the LOR-1-producing cells produced excessive amounts of collagen fibers. Tumors deriving from the LOR-1 producing tumors grew much more slowly than those that lacked this protein, but they displayed a much greater ability to spread. The tissue culture results were complemented by examination of tumors from cancer patients. Those with localized, benign tumors generally did not produce LOR-1, while those with malignant tumors always produced large amounts of the protein.

"Now that we know that the product of the very same gene produces collagen fibers and allows the cancer to metastasize, we are closer to understanding why this happens,” said senior author Dr. Gera Neufeld, a professor in the department of cell biology and anatomy at the Technion. The investigators are now searching for chemical compounds that could prevent metastasis by inhibiting the activity of LOR-1.





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