Complexity of tumor vasculature in clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has achieved some effectiveness against this unique malignancy. The complexity of the tumor vasculature in CCRCC has led to differences in correlating tumor microvessel density with patient prognosis. The authors' recent findings demonstrated that there were at least 2 major categories of tumor vessels in CCRCC-namely, undifferentiated and differentiated-correlating with patient prognosis in contrasting ways, with higher undifferentiated vessel density indicating poorer prognosis, and higher differentiated vessel density correlating with better prognosis. Furthermore, the presence of pericytes supporting the differentiated vessels varied in CCRCC. The distributions of pericyte coverage and differentiated vessels in CCRCC were uneven. The tumor margin had a higher pericyte coverage rate for differentiated vessels than did the inner tumor area. The uneven distributions of pericyte coverage and differentiated vessels in CCRCC prompted the authors to revisit the mechanism of tumor central necrosis, which was also known to be a prognostic indicator for CCRCC. The discrepancy of prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor in CCRCC was discussed. The complexity of the tumor vasculature in CCRCC also led the authors to begin to re-evaluate the therapeutic effects of antiangiogenic agents for each type of tumor vessel, which will in turn significantly broaden understanding of tumor angiogenesis and improve therapeutic effect. Clear cell renal cell carcinoma (CCRCC) is a highly vascularized malignancy. As evaluated by 2-phase multidetector computed tomography angiography, CCRCC is found to be able to develop an aberrant capsular vascular supply with outflow through an ovarian vein or testicular vein, 1 although positron emission tomography shows that blood perfusion of the tumor is reduced compared with normal kidney tissues. 2 Our expression profiling study also indicated that the expression level of vascular endothelial growth factor (VEGF; a potent proangiogenesis factor) in CCRCC is 5-fold higher than in other types of kidney

Rho GDP dissociation inhibitor‑β in renal cell carcinoma

“…HIF accumulation results in the overexpression of a variety of growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which promote neoangiogenesis (27). It is well known that the type and density of vasculature in RCC are associated with tumor histological grade and extent of macroscopic tumor necrosis, which affect the clinical course of RCC (28), including the ccRCC subgroup (29). Increased understanding of the molecular aspects of angiogenesis in tumor tissues has led to the development of targeted therapy for RCC (30), which is a highly-vascularized tumor entity (29).…”

“…It is well known that the type and density of vasculature in RCC are associated with tumor histological grade and extent of macroscopic tumor necrosis, which affect the clinical course of RCC (28), including the ccRCC subgroup (29). Increased understanding of the molecular aspects of angiogenesis in tumor tissues has led to the development of targeted therapy for RCC (30), which is a highly-vascularized tumor entity (29). Sunitinib, one of the first novel therapeutic agents to be used for RCC, modulates the VEGF-C pathway (31).…”

The Expression of Histone Demethylase JMJD1A in Renal Cell Carcinoma

“…But, most of RCC patients have been resistant to classic treatments such as chemotherapy, radiotherapy and hormonal therapy, so it is important to understand the RCC development and search for new treatment modalities [21]. Histone modifications such as acetylation and methylation have important regulatory roles for processes such as gene transcription and DNA damage repair, and misregulation of histone modification actively contributes to human cancer [22].Many histone demethylases such as KDM5B(JARID1B/PLU-1), and KDM8 which belong to iron-and 2-oxoglutarate-dependent dioxygenases are involved in cancer development including prostate cancer and breast cancer [23][24][25].…”

Presence of Tumour-infiltrating FOXP3+Lymphocytes Correlates with Immature Tumour Angiogenesis in Renal Cell Carcinomas

“…For most of solid tumours, microvessel density (MVD) correlates with poor prognosis. However, MVD remains a controversial prognostic predictor for RCC (Kirkali et al, 2001;Sabo et al, 2001a;Suzuki et al, 2001;Dekel et al, 2002;Kinouchi et al, 2003;Yildiz et al, 2008;Qian et al, 2009), a significant contributory factor being that blood vessels in RCC may be regarded as being monolithic in structure and function, which might not accurately reflect the functional diversity based on microvessel differentiation and location. Mature blood vessels are usually covered by pericytes, and pericyte coverage is regarded as an indicator of vascular maturation (Gerhardt and Semb, 2008).…”