The Mutually Mediated Chloride Intracellular Channel Protein 1 (CLIC1) Relationship between Malignant Cells and Tumor Blood Vessel Endothelium Exhibits a Significant Impact on Tumor Angiogenesis, Progression, and Metastasis in Clear Cell Renal Cell Carcinoma (ccRCC)

Abstract

Background: Overexpression of chloride intracellular channel protein 1 (CLIC1) in tumor cells has been confirmed, but it has received less attention in the tumor blood vessel endothelium. Aim. The assessment of CLIC1 expression in ccRCC tumor blood vessels and its relationship with TNM parameters and tumor cell CLIC1 expression. Methods: CLIC1 immunostaining in ccRCC was evaluated in 50 cases in both malignant cells and tumor blood vessels (CLIC1 microvessel density-CLIC1-MVD) and was correlated with TNM staging parameters. Results: CLIC1-MVD was observed in approximately 65% of cases, and CLIC1 co-localization in both tumor and endothelial cells was observed in 59% of cases. ccRCC was classified into four groups (Classes 0–3) based on the percentage of positive tumor cells, with each group including sub-groups defined by CLIC1 expression in the endothelium. Class 3 (60–100% positive tumor cells) had the highest CLIC1-MVD, with an impact on T and M parameters (p value = 0.007 for T, and p value = 0.006 for M). For cases with CLIC1 intracellular translocation, there was a strong correlation between CLIC1-MVD and M (p value < 0.001). Conclusions. Co-expression of ccRCC tumor and endothelial cells promotes tumor progression and metastasis and should be investigated further as a potential therapeutic target for ccRCC and other human malignancies.

Chloride intracellular channels in oncology as potential novel biomarkers and personalized therapy targets: a systematic review

“…Furthermore, CLIC1 expression significantly correlated with metastasis in G3 tumors. In another study, Ferician et al found CLIC1 expression in both ccRCC tumors and tumor vessels endothelium [21]. The authors classified the study group depending on CLIC1 expression in the tumor and in the tumor vessels.…”

A CLIC1 network coordinates matrix stiffness and the Warburg effect to promote tumor growth in pancreatic cancer

“…This conclusion is also supported Based on previous research, CLIC1 is upregulated in various malignant tumors, and its expression is associated with poor outcomes [19][20][21] . Aberrant CLIC1 expression endows tumor cells with high motility and invasiveness, making it a significant contributor to tumor invasion, metastasis, and angiogenesis [39][40][41] . In our study, we found that CLIC1 plays a critical role in cell-extracellular matrix interactions but differs in that it is a key molecule linking matrix stiffness and glycolysis.…”

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response

“…During postnatal life, CLIC1 expression in the kidney is present both in renal epithelial cells and stromal vascular endothelial cells. CLIC-1 is retained and overexpressed by cc-RCC tumor cells during malignant transformation, with its expression also observed on the stromal tumor blood vessel endothelium ( 112 ) ( Figure 3A ). Researchers detected isolated CLIC1-positive cells inside the tumor stroma as well as in between tumor cells ( 112 ).…”

“…CLIC-1 is retained and overexpressed by cc-RCC tumor cells during malignant transformation, with its expression also observed on the stromal tumor blood vessel endothelium ( 112 ) ( Figure 3A ). Researchers detected isolated CLIC1-positive cells inside the tumor stroma as well as in between tumor cells ( 112 ). Researchers did not study the involvement of isolated CLIC1-positive stroma cells with endothelial morphology in the local initiation of tumor stroma vasculogenesis.…”