Cell signalling molecule mediates obesity-associated cancer

Researchers from the University of Texas’s Health Science Center studying cancer metabolism have found that the utilisation of excessive adipose (fat) tissue by certain cancer cells is triggered by high levels of one particular signalling molecule in fat cells.
The research team, co-led by scientists from the MD Anderson Cancer Center, had previously established that excessive fat tissue can fuel the growth of certain cancers.
Their recent findings, published in the journal Nature Communications, uncover one molecular mechanism involved in that process that could lead to the development of new cancer treatment for obesity-associated malignancy.
The metabolism of a vast majority of aggressive cancers relies upon what is known as the ‘Warburg effect’, whereby cancer cells default into using glucose for rapid energy demand.
However, in obesity-associated prostate cancer, breast cancer and colorectal cancer, that the research scientists focused o, the tumours’ supply of nutrients also depends upon adequate vascularisation around the tumours.
The researchers noticed that in order to grow aggressively, these tumours can produce sufficient energy with a particular type of fat cells found in white adipose tissue called Adipose stromal cells (ASCs) that support tumour-nourishing blood vessels.
The scientists were able to identify chemokine CXCL1 as a key signalling molecule that regulates cell trafficking and the recruitment of ASCs by tumours that promote their progression.
When overexpressed in obese patients with prostate cancer, CXCL1 is thought to stimulate and attract ASCs through its receptors in the endothelial cells, enabling tumour vascularisation and growth.
The hypothesis was first tested in mouse models with prostate cancer. When the researchers silenced chemoline CXCL1, the obesity-induced progression of the cancer slowed.
To see whether their findings applied to humans, they also compared the CXCL1 levels in the tumours of obese and non obese patients. The team found that obese patients with prostate cancer had higher levels of CXCL1.
The study findings show that maintaining a healthy body weight as well as developing new strategies based on drugs depleting ASC or blocking CXCL1 could help reduce prostate cancer mortality.