Ovarian cancer metastases influenced by factors in target tissues
Both milky spots and fat cells in the omentum promote cancer cell migration, growth, and spread, reports new research. Results from a series of experiments have suggested a two-step model of omental colonization: (1) cancer cells are attracted to and lodge within immune cell-containing structures known as milky spots, and (2) fat storage cells (adipocytes) fuel cancer cell growth and spread.
Ovarian cancer was diagnosed in almost 23,000 women in the United States in 2012, and 16,000 died from the disease. The omentum, which this study found to be involved in metastases of ovarian cancer, is a large fatty structure that drapes off the stomach and blankets the peritoneal organs. Omental fat is composed of adipocytes, blood vessels, immune cells, and other connective tissue. It contains unusual immune cell-containing structures known as milky spots, which play a key role in many of its protective functions.
The first experiment of this study investigated whether abdominal fat tissue that contains milky spots is a more attractive target for cancer cells than abdominal fat that does not contain milky spots. Using ovarian cancer cell lines and mice, the ovarian cancer cell lines were found to form large lesions of cancer cells within milky spots. In contrast, ovarian cancer cells were rarely detected in abdominal fat that lacks milky spots.
Since ovarian cancer cells were rapidly localized to milky spots, the researchers hypothesized that omental tissues secrete one or more factors that attract cancer cells to these structures. Tissues containing milky spots were found to condition growth media to stimulate the migration of cancer cells. Cell migration increased by 95-fold in cell media conditioned by omenta and splenoportal fat, which in mice also contains milky spots. Notably, the ovarian cancer colonization of milky spots was not affected by deficiencies or the absence of T cells, B cells, and/or NK cells.
As ovarian cells grew, adipocytes were found to be depleted of lipids. This finding was consistent with previous studies, indicating cancer cells use lipids stored in adipocytes as an energy source for their continued growth, explained senior author Carrie Rinker-Schaeffer, PhD, of The University of Chicago in Illinois. The study was published in The American Journal of Pathology (2013;183(2):576-591).