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Updated: Mar 8, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Prostaglandin E2 receptor 4 mediates renal cell carcinoma intravasation and metastasis
Yushan Zhang1, Hamsa Thayele Purayil1, Joseph B Black1
1Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Abstract:
Treatment options for metastatic renal cell carcinoma (RCC) are limited. In this study, we investigated impact of prostaglandin E2 (PGE2) receptor 4 (EP4) on RCC metastasis. We found that knockdown of EP4 in two RCC cell lines, ACHN and SN12C, does not affect xenograft tumor take or growth rate in mice, but reduces metastasis by decreasing tumor intravasation. Using chick chorioallantoic membrane (CAM) assay, we confirmed that blockade of EP4 signaling inhibits tumor intravasation. In vitro studies associated EP4 expression and activity with RCC cell transendothelial migration (TEM). Gene expression analysis and validation assays showed that EP4 knockdown decreases expression of CD24, a ligand to the adhesion molecule P-selectin. Forced expression of CD24 in EP4 knockdown RCC rescues TEM capacity of the cells. Pharmacologic inhibition or knockdown of endothelial P-selectin blocks EP4-mediated cancer cell TEM, and inhibition of P-selectin prevents RCC tumor intravasation in CAM assay. Our results demonstrate that inhibition of EP4 attenuates the RCC intravasation and metastasis by downregulating CD24 and that P-selectin participates in tumor intravasation, implying a potential for these molecules as therapeutic targets for advanced RCC treatment.
Insights
Targeting prostaglandin E2 receptor 4 (EP4) can reduce metastatic renal cell carcinoma (RCC) spread. Inhibiting EP4 lowers cancer cell invasion and metastasis by downregulating CD24 and P-selectin, offering new therapeutic avenues.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis Research
Background:
- Metastatic renal cell carcinoma (RCC) presents limited treatment options.
- Prostaglandin E2 (PGE2) receptor 4 (EP4) role in RCC metastasis is not well understood.
Purpose of the Study:
- To investigate the impact of EP4 on RCC metastasis.
- To elucidate the molecular mechanisms by which EP4 influences cancer cell invasion.
Main Methods:
- Investigated EP4 knockdown effects on RCC cell lines (ACHN, SN12C) in vivo (xenografts) and in vitro (transendothelial migration assays).
- Utilized chick chorioallantoic membrane (CAM) assay to assess tumor intravasation.
- Analyzed gene expression changes, focusing on CD24 and P-selectin interactions.
Main Results:
- EP4 knockdown reduced RCC metastasis in mice without affecting tumor growth.
- EP4 signaling blockade and EP4 knockdown inhibited tumor cell intravasation and transendothelial migration (TEM).
- EP4 knockdown decreased CD24 expression, a P-selectin ligand, and P-selectin inhibition blocked EP4-mediated TEM and RCC intravasation.
Conclusions:
- EP4 inhibition attenuates RCC intravasation and metastasis by downregulating CD24.
- P-selectin plays a crucial role in RCC tumor intravasation.
- EP4, CD24, and P-selectin represent potential therapeutic targets for advanced RCC treatment.
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