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A New Source of Cancer in the Ovary

Stem cells  of the ovarian surface epithelium express LGR5 (green) in the hilum region of the ovary. Blue, nuclear stain DAPI. Laboratory of Dr. Alexander Nikitin.Combining efforts, a team led by Alex Nikitin, M.D., Ph.D., of Cornell University, in collaboration with the lab of Grigori Enikolopov, Ph.D., of Cold Spring Harbor Laboratory, identified a new stem cell niche in mouse ovarian epithelium.  Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women.  Despite this, the cell origin of these cancers is unknown.  Drs. Nikitin and Enikolopov now characterize a potential source of EOCs in mice.  This new source, the hilum, harbors a small population of cells responsible for regenerating the ovarian epithelium after it ruptures during ovulation.  Cells of the hilum bear the hallmarks of stem cells, they express specific stem cell markers, cycle slowly, and self-renew repeatedly over long periods of time.  However, hilum cells are also prone to transformation into cancer cells after inactivation of two well-known tumor suppressor genes, Trp53 and Rb1.  These same two genes are frequently found mutated in human ovarian cancers.  The identification of this stem cell niche, and its potential involvement in cancer, provides opportunities to better understand, and treat, ovarian cancers.

This work was supported by NYSTEM awards to Drs. Nikitin (C023050, C028125) and Enikolopov (C024323), and a NYSTEM shared facilities award to Cornell (C026718).

Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY.  Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.  Nature. 2013 Mar 14;495(7440):241-245.

Image: Stem cells of the ovarian surface epithelium express LGR5 (green) in the hilum region of the ovary. Blue, nuclear stain DAPI. Laboratory of Dr. Alexander Nikitin.