angiogenin and Kidney-Neoplasms

A hallmark of clear cell renal cell carcinoma (ccRCC) is the presence of intracellular lipid droplets (LD) and it is assumed that phosphatidic acid (PA) produced by phospholipase D (PLD) plays some role in the LD formation. However, little is known about the significance of PLD in ccRCC. In this study, we examined the expression levels of PLD in ccRCC. The classical mammalian isoforms of PLD are PLD1 and PLD2, and the levels of both mRNA were higher at the primary tumor sites than in normal kidney tissues. Similarly, both PLD were significantly abundant in tumor cells as determined by analysis using immunohistochemical staining. Importantly, a higher level of PLD was significantly associated with a higher tumor stage and grade. Because PLD2 knockdown effectively suppressed the cell proliferation and invasion of ccRCC as compared with PLD1 in vitro, we examined the effect of PLD2 in vivo. Notably, shRNA-mediated knockdown of PLD2 suppressed the growth and invasion of tumors in nude mouse xenograft models. Moreover, the higher expression of PLD2 was significantly associated with poorer prognosis in 67 patients. As for genes relating to the tumor invasion of PLD2, we found that angiogenin (ANG) was positively regulated by PLD2. In fact, the expression levels of ANG were elevated in tumor tissues as compared with normal kidney and the inhibition of ANG activity with a neutralizing antibody significantly suppressed tumor invasion. Overall, we revealed for the first time that PLD2-produced PA promoted cell invasion through the expression of ANG in ccRCC cells.

Topics: Aged; Animals; Carcinoma, Renal Cell; Cell Line, Tumor; Disease Progression; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Kaplan-Meier Estimate; Kidney Neoplasms; Mice, Nude; Middle Aged; Phospholipase D; Ribonuclease, Pancreatic; RNA Interference; RNAi Therapeutics; Xenograft Model Antitumor Assays

Tumour progression requires the presence of a rich vascular supply. A number of cytokines, chemokines and proteases participate in the process of tumour angiogenesis. We evaluated serum levels of angiogenin, panGRO (Growth Related Oncogene) (CXCL 1,2,3) and ENA-78 (Epithelial Neutrophil Activating) (CXCL5) in the serum of 32 patients with RCC (renal cell carcinoma) and 14 healthy blood donors by means of a protein array analysis. The patients were divided into three groups according to their disease stages (I+II, III, IV). We discovered significant differences between the blood donors and patients with RCC both in pre-operative and post-operative angiogenin, panGRO and ENA-78 levels. The increase in angiogenic factors lasted in patients even without metastases 2 months after surgery. We found no correlation between the levels of angiogenin and stages I+II, III and IV RCC. Patients with advanced carcinoma (stage III) had pre-operatively higher serum levels of ENA-78 than patients with stages I+II (p = 0,009) and IV (p< 0.001). Eight weeks after surgery the patients with stages I+II had significantly higher levels of panGRO than patients with stage IV.

Topics: Adult; Aged; Angiogenesis Inducing Agents; Carcinoma, Renal Cell; Chemokine CXCL1; Chemokine CXCL5; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Ribonuclease, Pancreatic

Angiogenesis, that is new blood vessel formation, is a prerequisite for growth and metastasis of solid tumors. This study was undertaken to quantify tumor capillaries, investigate immunohistochemical expression and measure serum concentrations of angiogenic growth factors in patients with Wilms tumor.. The hospital records of 33 patients were reviewed and new slides were stained for the endothelial cell marker CD31. Capillaries were quantified in the most vascularized part of the tumor (hot spot) and in the whole slide. New slides were stained immunohistochemically for the angiogenic growth factors angiogenin, basic fibroblast growth factor (bFGF), transforming growth factor alpha, transforming growth factor beta1-3, tumor necrosis factor alpha and vascular endothelial growth factor (VEGF), and their immunoreactivity was quantified. Pretreatment serum samples from 14 patients and 56 healthy control children were analyzed using enzyme-linked immunosorbent assay kits for angiogenin, basic fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, tumor necrosis factor alpha and VEGF.. Logistic regression analysis and Kaplan-Meier estimates showed that quantifications based on the tumor hot spot had a significant impact on survival probability (p <0.05). The tumor hot spot counts were highest in the blastemal compartment. Levels of hepatocyte growth factor and VEGF in serum were 3 times higher than those in controls (p <0.01).. Although the sample size is small in this study, the results imply that angiogenesis in Wilms tumor is driven by angiogenic growth factors, and that intratumoral capillary quantification and determinations of serum levels of angiogenic growth factors may be of clinical value.

Topics: Child; Child, Preschool; Endothelial Growth Factors; Female; Fibroblast Growth Factor 2; Hepatocyte Growth Factor; Humans; Immunohistochemistry; Infant; Infant, Newborn; Kidney Neoplasms; Logistic Models; Lymphokines; Male; Neovascularization, Pathologic; Prognosis; Retrospective Studies; Ribonuclease, Pancreatic; Transforming Growth Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Wilms Tumor