Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression
Prostate-specific membrane antigen (PSMA) protein expression is induced during prostate cancer progression and metastasis. Recently, we reported that PSMA-positive vesicles released by prostate cancer cell lines enhanced vascular endothelial cell angiogenesis and that PSMA may be involved in tumor a...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/3/165 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850200221391257600 |
|---|---|
| author | Ryuta Watanabe Keito Kagimoto Mami Chosei Tomohisa Sakaue Mie Kurata Noriyoshi Miura Riko Kitazawa Tadahiko Kikugawa Shigeki Higashiyama Takashi Saika |
| author_facet | Ryuta Watanabe Keito Kagimoto Mami Chosei Tomohisa Sakaue Mie Kurata Noriyoshi Miura Riko Kitazawa Tadahiko Kikugawa Shigeki Higashiyama Takashi Saika |
| author_sort | Ryuta Watanabe |
| collection | DOAJ |
| description | Prostate-specific membrane antigen (PSMA) protein expression is induced during prostate cancer progression and metastasis. Recently, we reported that PSMA-positive vesicles released by prostate cancer cell lines enhanced vascular endothelial cell angiogenesis and that PSMA may be involved in tumor angiogenesis. Similarly, it is known that PSMA is upregulated in peritumoral vessels in renal cell carcinoma (RCC). In this study, we investigated the significance and molecular function of PSMA in RCC. PSMA immunohistochemical staining confirmed PSMA presence only in perinephric tumor vessels, and PSMA intensity was strongly correlated with recurrence rate and venous invasion. Spatial gene expression analysis revealed that FOLH1 expression, which codes PSMA, was upregulated in tumor blood vessels around renal cancer, and that angiogenesis-related pathways were enhanced. The 10,000 g pellet fraction of the renal cancer cell lines Caki1- and ACHN-conditioned medium (CM) induced PSMA positivity in human umbilical vein endothelial cells (HUVECs) and enhanced tube formation. Mass spectrometry indicated that the 10,000 g pellet fraction contained various kinds of growth factors, like GDF15 and MYDGF. RNA sequencing showed that supplementing HUVECs with RCC cell CM-enhanced angiogenesis-related signaling pathways. Conclusively, microvesicle components secreted by RCC cells transform vascular endothelial cells into PSMA-positive cells, enhancing angiogenesis. |
| format | Article |
| id | doaj-art-58dfdeebdc4a4a9384851ec2de4e22e0 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-58dfdeebdc4a4a9384851ec2de4e22e02025-08-20T02:12:24ZengMDPI AGCells2073-44092025-01-0114316510.3390/cells14030165Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor ProgressionRyuta Watanabe0Keito Kagimoto1Mami Chosei2Tomohisa Sakaue3Mie Kurata4Noriyoshi Miura5Riko Kitazawa6Tadahiko Kikugawa7Shigeki Higashiyama8Takashi Saika9Department of Urology, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Urology, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Analytical Pathology, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Urology, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDivision of Diagnostic Pathology, Ehime University Hospital, Toon 791-0295, JapanDepartment of Urology, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon 791-0295, JapanDepartment of Urology, Ehime University Graduate School of Medicine, Toon 791-0295, JapanProstate-specific membrane antigen (PSMA) protein expression is induced during prostate cancer progression and metastasis. Recently, we reported that PSMA-positive vesicles released by prostate cancer cell lines enhanced vascular endothelial cell angiogenesis and that PSMA may be involved in tumor angiogenesis. Similarly, it is known that PSMA is upregulated in peritumoral vessels in renal cell carcinoma (RCC). In this study, we investigated the significance and molecular function of PSMA in RCC. PSMA immunohistochemical staining confirmed PSMA presence only in perinephric tumor vessels, and PSMA intensity was strongly correlated with recurrence rate and venous invasion. Spatial gene expression analysis revealed that FOLH1 expression, which codes PSMA, was upregulated in tumor blood vessels around renal cancer, and that angiogenesis-related pathways were enhanced. The 10,000 g pellet fraction of the renal cancer cell lines Caki1- and ACHN-conditioned medium (CM) induced PSMA positivity in human umbilical vein endothelial cells (HUVECs) and enhanced tube formation. Mass spectrometry indicated that the 10,000 g pellet fraction contained various kinds of growth factors, like GDF15 and MYDGF. RNA sequencing showed that supplementing HUVECs with RCC cell CM-enhanced angiogenesis-related signaling pathways. Conclusively, microvesicle components secreted by RCC cells transform vascular endothelial cells into PSMA-positive cells, enhancing angiogenesis.https://www.mdpi.com/2073-4409/14/3/165tumor angiogenesis of renal cell carcinomaprostate-specific membrane antigentumor endothelial cellshuman umbilical vascular endothelial cellstube formationkidney cancer surgically resected specimen |
| spellingShingle | Ryuta Watanabe Keito Kagimoto Mami Chosei Tomohisa Sakaue Mie Kurata Noriyoshi Miura Riko Kitazawa Tadahiko Kikugawa Shigeki Higashiyama Takashi Saika Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression Cells tumor angiogenesis of renal cell carcinoma prostate-specific membrane antigen tumor endothelial cells human umbilical vascular endothelial cells tube formation kidney cancer surgically resected specimen |
| title | Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression |
| title_full | Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression |
| title_fullStr | Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression |
| title_full_unstemmed | Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression |
| title_short | Vesicles Secreted by Renal Cell Carcinoma Cells Cause Vascular Endothelial Cells to Express PSMA and Drive Tumor Progression |
| title_sort | vesicles secreted by renal cell carcinoma cells cause vascular endothelial cells to express psma and drive tumor progression |
| topic | tumor angiogenesis of renal cell carcinoma prostate-specific membrane antigen tumor endothelial cells human umbilical vascular endothelial cells tube formation kidney cancer surgically resected specimen |
| url | https://www.mdpi.com/2073-4409/14/3/165 |
| work_keys_str_mv | AT ryutawatanabe vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT keitokagimoto vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT mamichosei vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT tomohisasakaue vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT miekurata vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT noriyoshimiura vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT rikokitazawa vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT tadahikokikugawa vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT shigekihigashiyama vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression AT takashisaika vesiclessecretedbyrenalcellcarcinomacellscausevascularendothelialcellstoexpresspsmaanddrivetumorprogression |