Intra-abdominal
tumors, such as
ovarian cancer, have a clear predilection for
metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why
tumor cells preferentially home to and proliferate in the omentum, yet omental
metastases typically represent the largest
tumor in the abdominal cavities of women with
ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of
ovarian cancer cells, and that
adipokines including
interleukin-8 (IL-8) mediate these activities. Adipocyte-
ovarian cancer cell coculture led to the direct transfer of
lipids from adipocytes to
ovarian cancer cells and promoted in vitro and in vivo
tumor growth. Furthermore, coculture induced lipolysis in adipocytes and β-oxidation in
cancer cells, suggesting adipocytes act as an energy source for the
cancer cells. A
protein array identified upregulation of
fatty acid-binding protein 4 (FABP4, also known as aP2) in omental
metastases as compared to primary ovarian
tumors, and FABP4 expression was detected in
ovarian cancer cells at the adipocyte-
tumor cell interface. FABP4 deficiency substantially impaired metastatic
tumor growth in mice, indicating that FABP4 has a key role in
ovarian cancer metastasis. These data indicate adipocytes provide
fatty acids for rapid
tumor growth, identifying lipid metabolism and transport as new targets for the treatment of
cancers where adipocytes are a major component of the microenvironment.