A protein called heregulin-, produced by cells in a normal nipple, has been identified as a substance that stimulates breast cancer cells to migrate to the nipple, resulting in Pagets disease of the breast.
Vera Schelfhout, M.D., and Christian De Potter, M.D., at the N. Goormaghtigh Institute for Pathology, University Hospital, Gent, Belgium, and colleagues, present the results of their research into the movement of these cancer cells in the April 19 issue of the Journal of the National Cancer Institute.
In Pagets disease of the breast, which occurs in about 1% of patients with breast cancer, the epidermis of the nipple is invaded by large breast cancer cells coming from an existing breast cancer. The authors sought to identify and characterize the "motility factor" released by normal nipple cells that might be involved in the penetration and migration of breast cancer cells through the nipple epidermis.
In brief, the investigators grew cultures of skin specimens from healthy adult donors and collected the medium in which these cells were grown. The expectation was that these cultures would have secreted any growth factor they produced into the medium. Various dilutions of this medium were then added to cultures of the human breast cancer cell line SK-BR-3. In the absence of added medium, cultured SK-BR-3 cells attached to a culture plate and remained spherical for 3 days. When diluted medium from the skin cultures was added, the SK-BR-3 cells become mobile.
Isolation and sequencing of the motility factor identified it as a protein named heregulin-. Further work proved that heregulin-
is produced by normal nipple skin cells and that it induces cell movement in specific types of human breast cancer cells (those overexpressing HER2/NEU proteins, which are receptors for heregulin-
). HER2/NEU receptors were found in Paget cell membranes in 26 of 30 tissue specimens from patients with Pagets disease, but they were not found in normal epidermal cells.
The authors conclude that heregulin-, a motility factor released by normal cells in the nipple, plays a key role in the development of Pagets disease. They suggest that this motility factor acts through various HER receptors (HER3 or HER4, as well as on their co-receptor HER2/NEU) on the cancer cells, resulting in the subsequent spread of the cancer cells throughout the nipple epidermis.
Contact: Dr. De Potter, Gent, Belgium, 329-240-3666; fax 329-240-4965.
Note: This memo to reporters is from the Journal staff and is not an official release of the National Cancer Institute (NCI) or Oxford University Press (OUP) nor does it reflect NCI or OUP policy. In addition, unless otherwise stated, all articles and items published in the Journal reflect the individual views of the authors and not necessarily the official points of view held by NCI, any other component of the U.S. government, OUP, or the organizations with which the authors are affiliated. Neither NCI nor any other component of the U.S. government nor OUP assumes any responsibility for the completeness of the articles or other items or the accuracy of the conclusions reached therein.
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