Targeting senescent adipocytes to treat tumour progression and metastasis in humans

Excess adipose tissue has been shown to increase the risk for many types of cancers and is associated with poor cancer outcomes. Obesity is increasing in epidemic proportions world-wide, with a concommitttant increase in obesity-associated cancer. Cancers not associated with overweight and obesity, however, are decreasing (US Cancer Statistics, 2017).

It is therefore essential to better understand the mechanisms whereby human fat cells contribute to cancer progression.

Adipocytes within the tumour microenvironment have been shown to promote cancer progression, however little is known about the contribution of adipose tissue distal to the tumour site.

With approximately 90% of the body’s fat being subcutaneous and metastasis a systemic disease, the contribution of this fat depot, in lean and obese states, is of prime importance.

This proposal uses technologies recently developed in the Spalding lab to better understand the unique contribution of human fat cellls to cancer metastasis.

We recently show that a subset of adipocytes in human adipose tissue senesce and secrete factors known to promote inflammation.

This proposal will investigate whether this sub-population of senescent fat cells, which increase in number in obese and hyperinsulinemic individuals, secrete factors which promote a metastatic phenotype (as indicated in unpublished data).

Targeting this population of fat cells, to mitigate the adverse effects of obesity on cancer progression, will be investigated.