Abstract 307P
Background
PSMA (prostate specific membrane antigen) protein expression increases with prostate cancer progression and metastasis. Recently, 68Ga-labeled PSMA PET has been used for the diagnosis of prostate cancer. Recently, we reported that PSMA-positive vesicles released by prostate cancer cell lines enhance the angiogenic activity of vascular endothelial cells and that PSMA may be involved in tumor angiogenesis. In this study, we focused on renal cell carcinoma and evaluated the correlation between PSMA expression in peritumoral vessels and prognosis in surgically resected renal cancer lesions.
Methods
We performed immunohistochemical staining of renal cell carcinoma tissues from 45 patients who underwent nephrectomy or partial nephrectomy at our hospital from January 2018 to December 2022, and evaluated the association between the intensity of PSMA expression in tumor vessels and recurrence rate. In addition, PSMA expression levels in human umbilical vein endothelial cells (HUVECs) supplemented with conditioned medium (CM) of renal cancer cell lines Caki1 and ACHN were detected by WB and IF, and angiogenic activity was assessed by tube formation assay. Gene expression changes in endothelial cells induced by vesicles secreted by renal carcinoma cells were analyzed by RNA-seq.
Results
Immunohistochemical staining for PSMA and CD31 confirmed that only perinephric tumor vessels were PSMA-positive; PSMA expression intensity was classified as weak (18 cases), moderate (11 cases), and strong (16 cases), and correlated with recurrence rate. When a 10,000 g pellet fraction of CM of a renal cancer cell line was added to HUVEC, it became PSMA positive and tube formation was enhanced. RNA-seq results showed that HUVECs supplemented with CM from a renal cancer cell line exhibited enhanced angiogenesis-related signaling pathways.
Conclusions
Microvesicle components secreted from renal carcinoma cells transform PSMA to vascular endothelial cells and enhance angiogenic activity. Future studies will elucidate the PSMA-positive process in normal vascular endothelial cells, which may lead to the development of novel anti-angiogenic drugs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Suzuki Urological Research Funding Foundation to RW, JSPS KAKENHI Grant Number 22K09529 to TK, JSPS KAKENHI Grant Number 21K09427 to NM.
Disclosure
All authors have declared no conflicts of interest.