Expression and roles of Slit/Robo in human ovarian cancer

Abstract

The Slit glycoproteins and their Roundabout (Robo) receptors regulate migration and growth of many types of cells including human cancer cells. However, little is known about the expression and roles of Slit/Robo in human ovarian cancer. Herein, we examined the expression of Slit/Robo in human normal and malignant ovarian tissues and its potential participation in regulating migration and proliferation of human ovarian cancer cells using two ovarian cancer cell lines, OVCAR-3 and SKOV-3. We demonstrated that Slit2/3 and Robo1 were immunolocalized primarily in stromal cells in human normal ovaries and in cancer cells in many histotypes of ovarian cancer tissues. Protein expression of Slit2/3 and Robo1/4 was also identified in OVCAR-3 and SKOV-3 cells. However, recombinant human Slit2 did not significantly affect SKOV-3 cell migration, and OVCAR-3 and SKOV-3 cell proliferation. Slit2 also did not induce ERK1/2 and AKT1 phosphorylation in OVCAR-3 and SKOV-3 cells. The current findings indicate that three major members (Slit2/3 and Robo1) of Slit/Robo family are widely expressed in the human normal and malignant ovarian tissues and in OVCAR-3 and SKOV-3 cells. However, Slit/Robo signaling may not play an important role in regulating human ovarian cancer cell proliferation and migration.

Prostaglandin F2 α upregulates Slit/Robo expression in mouse corpus luteum during luteolysis

“…The Slit/Robo family regulates cell fate, including migration, death, angiogenesis, and organogenesis (Wu et al 2001, Park et al 2003, Dickinson et al 2004, Hinck 2004, Koch et al 2011. It has been documented that Slit/Robo suppresses the development of cancers by inhibiting cell migration and promoting apoptosis (Dickinson et al 2008), and both Slits and Robos are inactivated in several tumors including cervical, prostatic, and ovarian tumors (Latil et al 2003, Singh et al 2007, Dai et al 2011.…”

Recent progress in histochemistry and cell biology

“…However, controversial roles with respect to cancer development have been reported, with Slit and Robo playing either the role of a tumor suppressor or tumor promoter. This prompted Dai et al (2011) to take up research on the roles of Slit and Robo (Slit 2/3 and Robo 1/4) in human ovarian cancer, a disease distinguished by a high mortality and a pathogenesis still poorly understood (Bast et al 2009). Expression studies were conducted on normal and malignant ovary tissues, as well as two human ovarian cancer cell lines (SKOV-3 and OVCAR-3).…”

Decreased Maternal Serum 2-Methoxyestradiol Levels are Associated with the Development of Preeclampsia

“…Thus, despite that mPE and sPE may have different pathogenesis [21,22], both mPE and sPE are associated with similar decreases in maternal serum 2-ME levels. These data suggest that such decreases might be their common features, and may serve as a serum diagnostic marker for PE in conjunction with other clinical diagnosis.…”

“…To explore the role of 2-ME in trophoblast cells, cell proliferation and migration were conducted using human trophoblast (HTR-8/SVneo) cell line, originally obtained from Dr. Charles H. Graham (Queen's University, Ontario, Canada) as described [21,22]. The HTR-8/SVneo cell, an immortalized extravillous cell line, is widely used as a trophoblast cell model for studying normal trophoblast function.…”