Vitamin D-mediated peritoneal repair can help prevent Ovarian cancer dissemination: Study

Mesothelial cells (MCs) play an important role in the spread of ovarian cancer (OvCa), and vitamin D-mediated peritoneal repair and normalization of thrombospondin-1 expression may be a unique technique for avoiding OvCa dissemination, finds a new study published in Matrix Biology Journal.

Ovarian cancer, a deadly gynecological disease, spreads to the peritoneum. Mesothelial cells operate as obstacles in the abdominal cavity, inhibiting cancer cells from adhering. However, in patients with OvCa, they undergo mesenchymal transition and turn into cancer-associated mesothelial cells (CAMs), providing a favorable milieu for tumors to promote metastasis. Attempts to restore CAMs to their original state, on the other hand, have been restricted. Kazuhisa Kitami and colleagues investigated whether vitamin D inhibited mesenchymal transition and restored MCs, thereby suppressing OvCa dissemination in vitro and in vivo.

The influence of vitamin D on the mutual interaction of MCs and OvCa cells was studied in vitro and in vivo utilizing xenograft models.

The key findings of this study were as follow:

1. Vitamin D recovered the CAMs, and thrombospondin-1 (an extracellular matrix component associated with a poor prognosis and detected in peritoneally metastasized OvCa) was found to increase OvCa cell adhesion and proliferation.

2. TGF-1 released by OvCa cells increased thrombospondin-1 expression in CAMs via Smad-dependent TGF- signaling.

3. Through vitamin D receptor/Smad3 competition, vitamin D hindered mesenchymal transition in MCs and decreased thrombospondin-1 expression, contributing to a significant decrease in peritoneal dissemination in vivo.

4. In preclinical models that mirror malignant peritonitis in vivo, vitamin D returned CAMs from a stable mesenchymal to an epithelial state and normalized thrombospondin-1 expression.

In conclusion, these findings emphasize MCs as critical factors of peritoneal dissemination and provide a viable approach for limiting peritoneal dissemination by blocking the interaction between OvCa cells and MCs. Researchers believe that repurposing vitamin D to restore peritoneal function and normalize THBS-1 expression might be a potential therapy for OvCa spreading.

Reference:

Kitami, K., Yoshihara, M., Tamauchi, S., Sugiyama, M., Koya, Y., Yamakita, Y., Fujimoto, H., Iyoshi, S., Uno, K., Mogi, K., Ikeda, Y., Yokoi, A., & Kajiyama, H. (2022). Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination via blockade of the TGF-β1/thrombospondin-1 axis. Matrix Biology: Journal of the International Society for Matrix Biology, 109, 70–90. https://doi.org/10.1016/j.matbio.2022.03.003