The p75 Neurotrophin Receptor`s Tumorigenic Properties in Ovarian Carcinoma

Introduction: Ovarian carcinoma (OC) is the most lethal gynecologic cancer. The p75 neurotrophin receptor (p75^NTR) belongs to the tumor necrosis factor receptor family. In some studies, p75^NTR is considered a pro-cancerous protein that promotes the malignant transformation of cells. It was also shown to induce secretion of exosomes, vesicles involved in cell-cell communication. Conversely, other studies suggested that p75^NTR might have anti-cancerous properties. Still, the precise roles of p75^NTR in the malignant transformation of cells in OC are unknown.

Methods: In order to achieve a better understanding regarding the role of p75^NTR in OC and its effect on tumorigenic behavior, we silenced this gene with the CRISPR/Cas9 system. KO clones were subjected to proliferation (MTT assay), migration (scratch assay), and MMP secretion (zymography assay) tests.

Results and discussion: We show that in the absence of the p75^NTR protein, the malignant behavior of OVCAR8 cells increases. We found in in vitro assays that the absence of p75^NTR has the remarkable ability to increase proliferation, migration, and MMP activity of cells. Furthermore, we found that there is a connection between p75^NTR and exosome secretion pathways, suggesting an additional antitumoral role for p75^NTR in OC.

Conclusion: Our results demonstrate that the p75^NTR protein acts as a suppressor of malignant behavior in this model, most likely by interacting with certain signaling pathways in this disease. Furthermore, p75^NTR may serve as an effective therapeutic target in OC.