Omental Adipocytes Play Key Role in Ovarian CA Metastasis
Tuesday, November 1, 2011 (Last Updated: 11/02/2011)
TUESDAY, Nov. 1 (HealthDay News) -- Primary human omental adipocytes promote homing, migration, and invasion of ovarian cancer cells to the omentum, and fatty-acid binding protein 4 (FABP4) seems to have a role in metastatic ovarian tumor growth, according to a letter published online Oct. 30 in Nature Medicine.
Kristen M. Nieman, Ph.D., from the University of Chicago, and colleagues investigated why tumor cell preferentially home to and proliferate in the omentum. Adipocytes were extracted and cocultured with ovarian cancer cells. Homing, adhesion, and tumor growth were measured in vitro and in vivo in mice.
The investigators found that homing, migration, and invasion of ovarian cancer cells was promoted by primary human omental adipocytes. These activities were mediated by adipokines, including interleukin-8. In adipocyte-ovarian cancer cell coculture, there was direct transfer of lipids from adipocytes to cancer cells, stimulating tumor growth in vivo and in vitro. In addition, coculture induced lipolysis in adipocytes and β-oxidation in cancer cells. Upregulation of FABP4 was identified in omental metastases compared to primary ovarian tumors, and FABP4 expression was seen in ovarian cancer cells at the adipocyte-tumor cell interface. In mice, FABP4 deficiency considerably impaired metastatic tumor growth.
"Our findings suggest that adipocytes act as major mediators of ovarian cancer metastasis to the omentum," the authors write. "FABP4, a mediator of lipid trafficking in adipocytes and potentially in tumor cells, may provide a therapeutic target to effectively impede intra-abdominal metastasis and growth."
One of the study authors has intellectual property pertaining to blocking FABP4 for the treatment of metastatic diseases.
Hematology & Oncology
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