The Influence of Mast Cell Mediators on Migration of SW756 Cervical Carcinoma Cells

Abstract

Abstract. The role of mast cell mediators on cervical cancer cell migration was assessed using an in vitro assay of scratch wound healing onto monolayers of HPV18-positive cervical carcinoma cells (SW756). Migration of SW756 cells was accelerated by co-culture with the mast cell line LAD2. This effect was inhibited by the H1R antagonist pyrilamine and the cannabinoid agonists 2-arachidonylglycerol (2AG) and Win 55,212-2. Therefore, the specific effects of histamine and cannabinoids on SW756 migration and LAD2 activation were analyzed. Histamine added to the in vitro assay of scratch wound healing either increased or inhibited SW756 migration rate by acting either on H1R or H4R, respectively. Cannabinoids acted on CB1 receptors to inhibit SW756 migration. Supernatants from SW756 cells stimulated LAD2 cell degranulation, which in turn was inhibited by cannabinoids acting via CB2 receptors. RT-PCR showed that SW756 expressed mRNA for CB1, CB2, H1R, H2R, and H4R. On the other hand, LAD2 expressed mRNA for all four HRs and CB2. The results suggest that mast cells could be contributing to cervical cancer cell invasion and spreading by the release of histamine and cannabinoids. Therefore, therapeutic modulation of specific mast cell mediators may be beneficial for cervical cancer treatment.

Histamine and Breast Cancer: A New Role for a Well Known Amine

“…Accordingly, the antiallergic compound tranilast inhibits cell migration and invasion in human malignant glioma cells blocking H1 receptors (Platten et al, 2001). A divergent response (stimulatory or inhibitory) on the migration rate of SW756 cervical carcinoma cells has been disclosed by histamine acting on H1 receptor or H4 receptor, respectively (Rudolph et al, 2008). However, as far as we know, our work is the first report about histamine-modulated migration and invasion through H4 and H2 receptors in breast tumor cells.…”

Histamine Receptors as Potential Therapeutic Targets for Cancer Drug Development

“…Histamine acting via H 1 R in cervical cancer cells could be pro-migratory, but when acting via H 4 R could inhibit migration. On the other hand, other results also showed that cervical carcinoma cell mediators can activate mast cells to degranulate, demonstrating an active and dynamic cross-talk between tumour cells and infiltrating mast cells as shown in morphologic studies of neoplastic tissues (Rudolph et al, 2008). In the light of these results, further investigations have to be done in order to elucidate the physiological role of histamine receptors on cell proliferation, as well as its implication in gynaecologic cancer progression with a potential interest for cancer treatment.…”

Antitumorigenic Effects of Cannabinoids beyond Apoptosis

“…Accordingly, mast cells were recently demonstrated as a source of promigrative chemoattractants acting as possible targets of cannabinoids (Rudolph et al, 2008). In the latter study, cancer cell migration initiated by mast cells was down-regulated by the endocannabinoid 2-arachidonylglycerol (2-AG) as well as by the synthetic cannabinoid WIN-55,212-2 in the scratch wound healing assay.…”