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Updated: Sep 5, 2025
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Suppressing MDSC Infiltration in Tumor Microenvironment Serves as an Option for Treating Ovarian Cancer Metastasis
Yichen Li1,2, Qian Zhang3, Mandi Wu1,2
1Department of Biomedical Sciences, JCC College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, China.
Abstract:
It is still a big puzzle how ovarian cancer cells and the tumor microenvironment (TME) attract lymphocytes infiltration for facilitating metastasis, a leading cause of death from gynecological malignancies. Using genome-wide LncRNA microarray assay, here we report that a LncRNA associated with ovarian cancer metastasis (LncOVM) is highly correlated with poor prognosis and survival. LncOVM interacts with and stabilizes PPIP5K2 by suppressing ubiquitinated degradation to promote complement C5 secretion from ovarian cancer cells. The TME-enriched complement C5 attracts myeloid-derived suppressor cells (MDSCs) infiltration in TME to facilitate metastasis. Knockdown of LncOVM or PPIP5K2 inhibits tumor progression in xenograft models. Application of C5aR antibody or inhibitor (CCX168) inhibits MDSC recruitment and restores the suppression of tumorigenesis and metastasis in vivo. Our study reveals that suppression of ovarian cancer metastasis can be achieved by targeting MDSC infiltration in TME through disrupting LncOVM-PPIP5K2-complement axis, providing an option for treating ovarian cancer patients.
Insights
This study identifies a novel long non-coding RNA (LncOVM) that promotes ovarian cancer metastasis by stabilizing PPIP5K2 and increasing complement C5 secretion. Targeting this axis inhibits myeloid-derived suppressor cells (MDSCs) and tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Ovarian cancer metastasis is a major cause of mortality in gynecological malignancies.
- The role of the tumor microenvironment (TME) and lymphocyte infiltration in ovarian cancer metastasis remains incompletely understood.
- Identifying novel molecular mechanisms driving metastasis is crucial for developing effective therapies.
Purpose of the Study:
- To elucidate the molecular mechanisms by which ovarian cancer cells and the TME promote metastasis.
- To identify novel long non-coding RNAs (lncRNAs) involved in ovarian cancer progression.
- To investigate potential therapeutic targets for suppressing ovarian cancer metastasis.
Main Methods:
- Genome-wide lncRNA microarray analysis to identify metastasis-associated lncRNAs.
- Investigated the interaction between LncOVM, PPIP5K2, and complement C5.
- Utilized xenograft models to assess the impact of LncOVM and PPIP5K2 knockdown on tumor progression.
- Evaluated the efficacy of C5aR antibody or inhibitor (CCX168) in blocking myeloid-derived suppressor cells (MDSCs) infiltration and tumor metastasis.
Main Results:
- A novel lncRNA, LncOVM, was identified and found to be highly correlated with poor prognosis and survival in ovarian cancer patients.
- LncOVM stabilizes PPIP5K2, leading to increased complement C5 secretion from ovarian cancer cells.
- The secreted complement C5 attracts MDSCs into the TME, promoting metastasis.
- Knockdown of LncOVM or PPIP5K2, or inhibition of C5aR, significantly suppressed tumor progression, MDSC recruitment, and metastasis in vivo.
Conclusions:
- The LncOVM-PPIP5K2-complement C5 axis plays a critical role in promoting ovarian cancer metastasis by facilitating MDSC infiltration in the TME.
- Targeting this axis, specifically by inhibiting MDSC recruitment, offers a promising therapeutic strategy for ovarian cancer treatment.
- Disrupting the LncOVM-PPIP5K2-complement axis presents a novel therapeutic option for patients with ovarian cancer.
