Editors' ChoiceOvarian Cancer

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Science Translational Medicine  16 Nov 2011:
Vol. 3, Issue 109, pp. 109ec185
DOI: 10.1126/scitranslmed.3003415

Ovarian cancer is often diagnosed at an advanced stage, when it is metastatic. The most common subtype of ovarian cancer (serous) frequently metastasizes to the omentum, which is a large fatpad that extends from the stomach, envelopes the bowel, and serves as an endocrine organ and storage for lipids.

The fact that ovarian cancer cells metastasize to the omentum more than any other site suggests that this characteristic is not random and that perhaps the microenviroment of the omentum—specifically, the adipocytes—might contribute to the metastatic phenotype.

Nieman et al. now report that primary human omental adipocytes promote the homing, migration, and invasion of ovarian cancer cells. When the researchers injected fluorescently labeled human ovarian cancer cells into female mice, most of the cancer cells homed to the omentum within 20 min. The scientists then discovered that purified human omental adipocytes—or omental adipocyte-conditioned medium—induced migration and invasion of the ovarian cancer cells in an in vitro assay. Further studies showed that cytokines secreted by omental adipocytes, including interleukin-8, mediate this migration.

In addition, coculturing of the adipocytes and ovarian cancer cells led to a direct transfer of lipids from the adipocytes to the cancer cells, suggesting that the omental adipocytes act as an energy source for the cancer cells.

The researchers then used a protein array to compare primary ovarian cancer tissue and omental metastatic tissue from women with serous carcinoma. They detected up-regulation of fatty-acid binding protein 4 (FABP4)—a protein previously shown to regulate lipolysis—in metastatic relative to primary ovarian tumors. When the investigators added a FABP4 inhibitor to cocultured adipocytes and ovarian cancer cells, they saw little accumulation of lipids in the cancer cells; furthermore, FABP4 deficiency in mice impaired ovarian cancer metastasis. These experiments suggest that FABP4 represents a new target for ovarian cancer therapeutics.

K. M. Nieman et al., Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498–1503 (2011). [Abstract]

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