Prolactin increases survival and migration of ovarian cancer cells: Importance of prolactin receptor type and therapeutic potential of S179D and G129R receptor antagonists

Variably-spliced prolactin receptors (PRLRs) and PRL are expressed by the ovarian cancer cell lines, TOV-112D, OV-90 and TOV-21G. Incubation in the PRLR antagonists, G129R- or S179D-PRL, or anti-PRL reduced cell number, indicating a functional autocrine PRL growth loop. Added PRL promoted, and the antagonists decreased, cell migration. When cells were stressed, added PRL decreased apoptosis and increased survival, and the antagonists had the opposite effect. Cells expressing higher long:short PRLR ratios had increased growth, survival and migration in response to PRL. Results suggest that PRLR antagonists may be therapeutically beneficial in ovarian cancer.

► Ovarian cancer cell lines express prolactin and prolactin receptors.
► A functional autocrine prolactin growth loop was demonstrated.
► Cells with high long: short prolactin receptor ratios had increased growth rates.
► Prolactin increased growth, survival and migration.
► Two prolactin receptor antagonists decreased growth, survival and migration.