Tuesday, January 12, 2016

Obesity and PCa

In a paper in Nature the authors provide a compelling analysis for the impact of fat cells via obesity and the development of aggressive PCa.

They state:

Obesity favours the occurrence of locally disseminated prostate cancer in the periprostatic adipose tissue (PPAT) surrounding the prostate gland. Here we show that adipocytes from PPAT support the directed migration of prostate cancer cells and that this event is strongly promoted by obesity. This process is dependent on the secretion of the chemokine CCL7 by adipocytes, which diffuses from PPAT to the peripheral zone of the prostate, stimulating the migration of CCR3 expressing tumour cells. In obesity, higher secretion of CCL7 by adipocytes facilitates extraprostatic extension. The observed increase in migration associated with obesity is totally abrogated when the CCR3/CCL7 axis is inhibited. In human prostate cancer tumours, expression of the CCR3 receptor is associated with the occurrence of aggressive disease with extended local dissemination and a higher risk of biochemical recurrence, highlighting the potential benefit of CCR3 antagonists in the treatment of prostate cancer.

This is not at all unanticipated.  The work does give a basis for the genomic characteristics of the process as well as describing a therapeutic target. Clinically this has often been observed. In addition obese patients also often have progression on a more aggressive manner. Clearly the fat cell mechanism as discussed is a viable and credible path. The aggressive oxidation effects may also play a role especially via methylation.

This is a strong and prescient paper and well worth following.