Adipose Tissue Support of Cancer Growth is Mediated by the Adipokine FABP4

Adipose tissue provides stromal support for tumor growth in many types of cancers by various secreted factors. Furthermore, adipose tissue dysfunction in obesity is an established risk factor not only for cardio-metabolic abnormalities, but also, as becoming increasingly evident, for increased cancer incidence and aggressiveness. Rapidly accumulating evidence suggest that the adipokine fatty acid binding protein 4 (FABP4), is an important facilitator of cancer growth and metastasis in various cancers.

Aim:
As the obesity-attributable cancer burden is likely to continue and rise, identifying FABP4 as a stromal secreted factor that promotes tumor growth represents an attractive target for pharmacological interventions in obesity-related cancers.

Methods:
We focused on two cancers that heavily depend on adipose tissue stromal support: pancreatic ductal adenocarcinoma (PDAC) that its incidence and pathogenesis are linked to obesity, and melanoma, for which the abundant adjacent sub-cutaneous adipose tissue provides key stromal support.

Results:
Both melanoma and PDAC cells proliferation and migration are markedly enhanced in-vitro by incubation with mouse adipose tissue condition medium, effects that are significantly inhibited when adipose tissue of Fabp4 knockout (Fabp4^-/-) mice is used. Furthermore, the in-vivo growth of melanoma or PDAC tumors is profoundly attenuated in Fabp4^-/- compared to wild-type mice. Unbiased approach to elucidate FABP4 mechanism of tumor support suggests an immune-modulatory role of suppressing antigen presentation by cancer cells, decreasing cytokine signaling and PTEN activation.

Conclusion:
Our preliminary results highlight the inhibition of FABP4 as a potential novel therapeutic approach that deprives tumors from this key stromal factor.