Spread of Breast Cancer Initiated by Signaling Molecule

Spread of breast cancer to distant parts of the body, a process called as metastasis, is initiated by a signaling molecule called transforming growth factor (TGF), researchers at Memorial Sloan-Kettering Cancer Center (MSKCC)have revealed.

The study, led by David Padua, a graduate student at MSKCC, mainly focussed on how cells in the body communicate with each other through cytokines, signalling molecules that direct a wide range of activities such as cell growth and movement.

Normally, a particular cytokine-TGF is responsible for suppressing tumour development. But, the findings of the study indicate that human cancer cells are capable in misusing these cytokines for their own gain by forcing TGF to enhance a tumour's ability to spread instead of suppressing it.

The scientists found that almost 50 percent of all breast tumours contained active TGF through computer-based analysis and also the affected tumours were found to be more aggressive and more likely to metastasize to the lung during the course of the patients' disease.

The next set of experiments were carried out on mice and it was found that TGF initiates breast cancer cells to make a second cytokine, called angiopoietin-like 4 (ANGPTL4), which enhances the ability of the cancer to spread to the lungs through the blood circulation. In fact, the results indicate that the breast cancer cells use ANGPTL4 to break down the thin capillaries of the lung, hence escaping into the lung tissue.

"Our work shows that TGF? enhances human breast cancer metastasis and reveals how tumor cells learn to exploit cytokines by making them work as a relay system to promote the spread of breast cancer," said senior author, Joan Massagu?, PhD, Chairman of the Cancer Biology and Genetics Program at MSKCC and a Howard Hughes Medical Institute investigator.

The researchers are evaluating ways to interfere with the action of these cytokines to prevent metastasis in cancer patients.

"Deciphering how cancer cells take advantage of these cytokines is essential for developing therapies that can prevent this process. Because cytokines act outside of cells they can be more easily targeted by drugs that block their activity," said Padua.

This research has implication in developing agents to interfere with TGF for prevention and treatment of cancer metastasis. It points at ANGPTL4 as a possible target to interrupt the TGF stimulus of metastasis without interfering with the molecule's beneficial effects.

Besides, many pharmaceutical companies are testing TGF-blocking compounds in clinical trials as candidate drugs against breast cancer, melanoma, and other types of cancer.

The study is published in the latest issue of Cell.

Source-ANI
RAS/L