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Engineering New Mammary Tissue

A FULLY functional breast has been grown from a stem cell found in female mice, in a study that promises insights into recurring breast tumours and a fresh approach to plastic surgery.
The research in Australia suggests that breast cancers may be triggered by rogue mammary stem cells that are difficult to kill with standard chemotherapy, and that later “reseed” the breast with tumour cells once a patient appears to be in remission.

If the findings prove applicable to people, scientists hope to develop drugs that target abnormal breast stem cells to eliminate not only tumours but also the source tissue from which they arise. In the longer term, it may also be possible to use mammary stem cells to grow breast tissue for reconstructive surgery after a mastectomy, or even for use in breast enhancement operations.

In the study, which is published today in the journal Nature, a team led by Jane Visvader, of the Walter and Eliza Hall Institute in Melbourne, isolated mammary stem cells from the breast pads of female mice for the first time.

They transplanted one of these cells into the mammary fat pad of a living female mouse from which all breast tissue had been removed. The cell divided and eventually gave rise to all the normal types of cell found in the mouse breast, and the gland worked normally to produce milk.

Researchers suspect that mammary stem cells play an important role in the genesis of some breast cancers. If a stem cell carries genetic errors, it may start producing cancerous breast cells, in effect becoming a “tumour factory”. This may be why some breast cancers return after apparently being eliminated by chemotherapy.

Chemotherapy targets fast-dividing cancer cells, but the stem cells may prove more resistant as they do not reproduce so quickly. This would mean that, although the primary breast cancer is killed by the treatment, abnormal stem cells are left behind to continue turning out cancer cells, restarting the tumour.

“The ultimate objective is to create a drug that will, in effect, switch off breast cancer cells,” Dr Visvader said. “To do this, the exact make-up of genes expressed by normal and rogue stem cells will need to be determined. Then a drug will be designed to engage with and neutralise the faulty feature of the stem cell.”

The team is now examining tissue from human breast tumours, to determine whether they share characteristics with the mouse model. A second team, from the British Columbia Cancer Research Centre in Vancouver, has also isolated mammary stem cells and published its work today in Nature.

The research could also have implications for plastic surgery. If women have similar breast stem cells, it may eventually be possible to grow them into breast tissue. This could be used to reconstruct the breasts of cancer patients who have had a mastectomy, or even to grow implants for augmentation operations.

Women who have breast cancer surgery fare much better if the surgeon has had plenty of practice, research by a team from Guy’s Hospital in London shows. The study of 1,351 women in South Korea, published in the International Journal of Clinical Practice, found that 95 per cent of those readmitted to hospital after surgery had been treated at units doing fewer than 100 such procedures a year.

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