Alveolar Soft Part Sarcoma - The Reverse Warburg Effect In Action?

Alveolar soft part sarcoma (ASPS) is a rare cancer - rare even among soft tissue sarcomas - that is slow growing but hard to treat. When the disease metastasises the prognosis is generally grim and there are few options for treatment if surgical resection is not possible. A new paper, published in the journal Cancer Cell, describes work in a mouse model of the disease which may ultimately have important therapeutic consequences.

A team at the University of Utah have created a mouse model of ASPS, by fusing two strands of DNA to create a fusion gene which forms tumours in the mice in which it is implanted. What's more the resulting disease behaves very much like ASPS in humans, including producing very similar genetic profiles. Intriguingly the mouse tumours formed preferentially in areas of the body which had high concentrations of lactate. In humans this tends to be in the skeletal muscles as lactate is a by-product when our muscles are straining for energy in low oxygen conditions. In the mice the areas with the highest lactate concentrations were in the skull.

Generally tumours are believed to generate excess lactate as a by-product of their metabolism - this is known as the Warburg effect. And yet here the tumours seem to be feeding off the lactate produced by non-cancer cells. As one of the researchers, Kevin Jones explains: "It's unusual to find a cancer using lactate this way. The ASPS cells grow preferentially where they are bathed in high concentrations of lactate."

The most likely explanation is that this is yet another example of the reverse Warburg effect, first described by Michael Lisanti and his team. This is a topic of huge importance as it revises what has been seen as a core component of our understanding of cancer. In this model of cancer, the tumour cells act on non-cancer cells to change their metabolism so that they emit lactate and glutamine, which the tumour cells use as a more powerful fuel source.

This does open up opportunities for intervention, however. If we can interrupt that 'metabolic shuttle' between lactate consuming tumour cells and stromal cells they are 'farming' then we can starve the cancer cells and so slow - or possibly even halt - tumour growth.