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17 January 2013

Body’s ibuprofen, SPARC, reduces inflammation and thus bladder cancer development and metastasis

Cancer researchers are increasingly aware that in addition to genetic mutations in a cancer itself, characteristics of the surrounding tissue can promote or suppress tumour growth.

One of these important tissue characteristics is inflammation – most cancers prosper in and attach to inflamed tissue and so many cancers have developed ways to create it.

A University of Colorado Cancer Center study published in the current issue of The Journal of Clinical Investigation shows that the protein SPARC (Secreted Protein Acidic and Rich in Cysteine) acts much like an anti-inflammatory drug, attempting to heal tissues inflamed by tumours. Likewise, cancers – for example, bladder cancer in this study – have developed ways to turn off the production of SPARC, thus allowing growth and metastasis, especially to the lung where bladder cancer is frequently fatal.

“In fact, we show the effects of SPARC go beyond even this anti-inflammatory role. Additionally, the protein is involved in disallowing migrating cancer cells from attaching at possible metastasis sites and stopping the production of new blood vessels needed to feed tumour tissue,” says Dan Theodorescu, director of the University of Colorado Cancer Center and the study’s senior author.

The study started by evaluating SPARC levels in human bladder cancer samples. In less aggressive cancers, both the tumour and the surrounding tissue made SPARC. In more aggressive cancers, it was just the surrounding tissue that made SPARC – the aggressive tumour itself had suppressed production of the protein. In these human bladder cancer tumours, more SPARC was associated with longer survival.

This distinction between SPARC made in the tumour and SPARC made in the surrounding tissue largely explains previous work that found high SPARC in aggressive tumours and so suggested a possible tumour-promoting role for the protein. Instead, it seems that surrounding healthy tissue may respond to a growing tumour by increasing SPARC production, which it hopes will mute the tumour. Thus high SPARC that is in fact an attempt at tumour suppression can be coincidentally associated with aggressive tumours when the entire tumour is examined. Healthy tissue turns up SPARC to mute tumours. Aggressive cancers turn down SPARC to promote tumours.

Then Theodorescu and colleagues turned to animal models without the ability to manufacture SPARC. Not only was bladder cancer quicker to develop in these models, but the cancer was also more likely to travel to invade lung tissue. When SPARC was added to these models, tumour growth and metastasis was reduced.

“This is a comprehensive portrait of SPARC function using human and murine bladder cancer as a model, and the first to clearly distinguish between the role of SPARC generated in the tumour and the role of the protein generated in the surrounding tissue,” says Theodorescu. “We hope this provides the rational basis for further exploring manipulation of SPARC as a therapeutic intervention.”

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