Patricia E. Gallagher, Ph.D., and E. Ann Tallant, Ph.D., scientists in the Hypertension and Vascular Research Centre at WFUBMC, demonstrated that the peptide angiotensin-(1-7) attacked breast cancer in two ways: by inhibiting the growth of the breast cancer cells themselves and by inhibiting the growth of cancer-associated fibroblasts (CAFs), cells found in the tumour microenvironment - the tissue surrounding the tumour. CAFs play a vital role in tumour initiation, growth and metastases by providing structural support for the tumour cells and by producing growth factors that help the tumour cells grow.
In this study, mice were injected with human breast cancer cells to form the two most common types of breast tumours - estrogen-receptor and HER2 sensitive. In women with breast cancer, an estimated 50 to 60% have estrogen-receptor sensitive tumours and 20 to 30% have HER2 sensitive tumours.
Once the tumours grew, the mice were injected with either angiotensin-(1-7) or saline for 18 days. In the mice treated with angiotensin-(1-7), there was a 40% reduction in tumour size as compared to the saline-injected mice, whose tumours grew three times their size at the initiation of treatment. Breast tumour fibrosis also was reduced by 64 to 75% in the mice treated with the peptide as compared to the saline-injected mice. Fibrosis is the thickening of the breast tissue around and within the tumour that acts as a scaffold to support the spread of cancer cells.
"This is the first study to show that angiotensin-(1-7) not only inhibits the growth of tumours, but also inhibits breast tumour fibrosis," Gallagher said. "Think of it as a seed and the soil around it - the seed being the tumour and the soil being the fibrosis. You can attack the seed, or you can attack the soil, or do both, and our drug does both."
The tumour microenvironment is especially important when the cancer has metastasised, Tallant said, because drugs that are effective for treating the primary tumour often are not effective in treating a tumour growing in a different part of the body. "Our findings also suggest that angiotensin-(1-7) may enhance the effect of chemotherapeutic agents when administered in combination with other drugs by altering the microenvironment in which the tumour grows," she said.
"Because the safety of angiotensin-(1-7) was established here at Wake Forest Baptist in a recently completed trial in patients with different types of solid tumours, we hope to go to clinical trials for breast cancer relatively soon," Gallagher said.
Gallagher's and Tallant's initial research conducted at the Comprehensive Cancer Centre at Wake Forest Baptist showed that angiotensin-(1-7) inhibited the growth of vascular smooth muscle cells, the cells that surround blood vessels and regulate blood pressure. Previous studies showed that patients treated with drugs to reduce blood pressure and increase angiotensin-(1-7), also had a smaller chance of developing cancer. Based on this information, Gallagher and Tallant studied the effect of the peptide on lung cancer and discovered that angiotensin-(1-7) inhibited the growth of lung tumours in mice, as well as reduced the supply of blood vessels to the growing tumour. Their latest study, as reported in Cancer Research, now shows additional effects of angiotensin-(1-7).
Both scientists and Wake Forest University Baptist Medical Centre hold a patent on the use of angiotensin-(1-7) for the treatment of cancer.
Source: Wake Forest University Baptist Medical Centre
