Regulation of Scatter Factor Expression in Breast Cancer

Eliot M. Rosen, M.D., Ph.D. Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, N.Y.

Dr. Eliot Rosen and colleagues, of Albert Einstein College of Medicine, New Hyde Park, N.Y., evaluated how scatter factor, a growth factor, may regulate the growth of human breast cancers. Greater knowledge of the mechanisms important for breast cancer development and progression is of keen scientific interest. Such information can provide insights to better understand the nature of the disease and to develop new therapies to prevent or halt its progression.

Most human breast cancer cells contain high levels of the receptor for scatter factor, which means that, in the laboratory, breast cancer cells will vigorously multiply in the presence of the growth factor. Dr. Rosen and his colleagues found that scatter factor causes human breast cancer cells to move faster and to be more invasive in cell cultures. The growth factor induces the breast cells to produce an enzyme that degrades tissue, they found, thus facilitating tumor invasion.

In laboratory animals, they found that scatter factor greatly stimulates the formation of new blood vessels (angiogenesis), an essential step for tumor growth and spread (metastasize). They also found that invasive breast cancer tissue samples with higher levels of scatter factor have higher levels of von Willebrand's factor (VWF), which is a protein produced by the lining of blood vessels. This suggests that higher levels of VWF may be associated with greater angiogenesis.

In other experiments, the investigators found that levels of scatter factor were significantly higher in invasive breast cancer tissue than in benign breast lesions or non-invasive breast cancers (ductal carcinoma in situ (DCIS)). Invasive breast cancers had nearly four times the scatter factor content of DCIS tissue. And tumors that had spread to the axillary lymph nodes had higher levels of scatter factor than invasive cancers that had not yet spread beyond the breast, although this difference was not as great as that seen between invasive breast cancers and DCIS tissue. Scatter factor levels did not vary by histologic (cell) type of invasive breast cancer.

Dr. Rosen and his colleagues also demonstrated in an animal model that scatter factor can stimulate the growth of human breast tumors. Human breast cancer cells altered so that they produced high levels of scatter factor were injected into mice. The researchers found that mammary (breast) tumors grew much more rapidly in these mice than in those that received unaltered breast cancer cells.

Tissue specimens from the Long Island Jewish Frozen Tumor Bank at Long Island Jewish Medical Center were used for the research.

Findings were reported in 1996. Since this study, Dr. Rosen has continued his research on scatter factor further advancing understanding of its role in tumor development.

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