Washington: A team led by an Indian-origin scientist has identified a group of little-explored cancer cells that may play a key role in preventing the progression of the disease, a finding they say could lead to re-evaluation of common cancer treatments for patients.
   
The study, published in the journal Cancer Cell, also suggested that anti-angiogenic therapies that target those tumour cells -- called pericytes -- may inadvertently be making tumours more aggressive and likely to spread.
   
Advanced drugs shrink tumours by cutting off their blood supply, but in doing so they wipe out pericytes that provide structural support to blood vessels and act as 'gatekeepers' to pen in cancer.
   
Conducted at Beth Israel Deaconess Medical Center in Boston, the study highlights the importance of more research on tumour-cell composition in order to devise more effective therapies, the researchers said.
   
"Not everything present in the tumour is bad for us. Pericyte functionality and coverage on blood vessels, is important because it allows the blood vessels to be leak-free and normal," said lead author Raghu Kalluri, a professor of medicine at Harvard Medical School.
   
The implications of this study show how today's practice of targeting pericytes as a form of treatment may come at a price, Kalluri explained.
   
For the study, Kalluri and his team created genetically modified mice to support drug-induced depletion of pericytes in growing tumours. They then deleted pericytes in their cancer tumours, reducing pericyte numbers by 60 percent.
   
Compared with wild-type controls, they saw a 30 percent decrease in tumour volumes over 25 days. However, contrary to conventional clinical wisdom, the investigators found that the number of secondary lung tumours in the engineered mice had increased threefold compared to the control mice, indicating that the tumours had metastasised.

"If you just look at tumour growth, the results were good. But when you look at the whole picture, inhibiting tumour vessels was not controlling cancer progression. The cancer was, in fact, spreading," said Kalluri.

Additional experiments showed that combining pericyte depleting drugs with the Met-inhibiting drug helped suppress EMT and metastasis.
   
To determine if the findings were relevant to patients, the scientists examined 130 breast cancer tumour samples of varying cancer stages and tumour sizes and compared pericyte levels with prognosis.
   
It was found that samples with low numbers of pericytes in tumour vasculature and high levels of Met expression correlated with the most deeply invasive cancers, distant metastasis and five and 10-year survival rates lower than 20 percent.
   
"These results are quite provocative and will influence clinical programs designed to target tumour angiogenesis," said Ronald DePinho, president of the University of Texas MD Anderson Cancer Center. "These impressive studies will inform and refine potential therapeutic approaches for many cancers."
   
Meanwhile, for Kalluri, the work suggests that certain assumptions about cancer must be revisited.
   
"We must go back and audit the tumour and find out which cells play a protective role versus which cells promote growth and aggression," he said, adding, "Not everything is black and white. There are some cells inside a tumour that are actually good in certain contexts."

(Agencies)