The Adipokine Fatty Acid Binding Protein 4 – Linking Obesity and Cancer

Obesity is an established risk factor not only for cardio-metabolic abnormalities, but also, as becoming increasingly evident, for increased cancer incidence and metastasis. Rapidly accumulating evidence suggest that fatty acid binding protein 4 (FABP4), secreted by adipocytes and other stromal cells, is an important facilitator of cancer growth and metastasis in many cancer types.

Given the growing body of evidence in support of an important role for FABP4 in various cancers, we have studied its potential pro-cancerous role in melanoma. Our in-vitro results demonstrate that melanoma cells proliferation and migration is markedly stimulated by incubation with mouse adipose tissue condition medium, effects that are significantly inhibited when adipose tissue of Fabp4 knockout (Fabp4^-/-) mice is used. Consistent with that, the in-vivo growth of melanoma tumors is profoundly attenuated in Fabp4^-/- compared to wild-type mice. Furthermore, FABP4 neutralization by a specific monoclonal antibody inhibits melanoma growth in-vivo. Unbiased approach to elucidate FABP4 mechanism of promoting tumor growth suggests an immune-modulatory role of suppressing antigen presentation by cancer cells, and decreasing cytokine signaling and PTEN activation.

As the obesity-attributable cancer burden is likely to continue and rise, identifying FABP4 as a stromal secreted factor with emerging role in promoting tumor growth may represents an attractive target for pharmacological interventions in the fight against cancer.