Major finding: Visceral adipocytes promote homing and growth of ovarian cancer cells.
Impact: A targetable mechanism underlying metastatic behavior of abdominal tumors is identified.
Concept: Adipocytes secrete cytokines to attract tumor cells and provide lipids as an energy source.
Tumors that metastasize to the abdominal cavity, such as ovarian, colon, and gastric cancers, preferentially metastasize to the omentum, a peritoneal organ largely composed of adipocytes. The mechanistic basis for this predilection is unknown. Nieman and colleagues report that adipocytes are instrumental in creating a microenvironment that promotes metastasis (tumor invasion and proliferation). The authors demonstrated that omental adipocytes attract ovarian cancer cells and promote migration and invasion by secreting cytokines. Neutralization of cytokines reduced in vivo homing of ovarian cancer cells to the mouse omentum, suggesting that adipocytes promote the early steps of metastasis. The authors also showed, using fluorescently labeled lipids, that adipocytes transfer fatty acids to cancer cells. Ovarian cancer cells metabolically adapt to the increased availability of lipids by increasing the rate of β-oxidation to utilize the energy from fatty acids for growth. A reverse-phase protein array identified fatty acid binding protein 4 (FABP4) as specifically upregulated in omental metastases, with immunohistochemical staining indicating strong expression at the adipocyte–cancer cell interface. Pharmacologic inactivation of FABP4 decreased cancer cell lipid accumulation and invasiveness in vitro, and deletion of Fabp4 in mice drastically reduced omental metastasis of ovarian cancer cells. Collectively, these data provide a rationale for why cancer cells metastasize to a lipid-rich microenvironment that may be applicable to other tumor types, and identify FABP4 as a potential anti-metastatic drug target.
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011;17:1498–503.
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