Chemokines and its receptors have significant impact on physiological and pathological processes and studies concerning their association with tumor biology are subject of great interest in scientific community. CXCL12/CXCR4 axis has been widely studied due to its significant role in tumor microenvironment, but it is also important to development and maintenance of tissues and organs, for example, in the brain and cerebellum. Studies have demonstrated that CXCL12 and CXCR4 are required for normal cerebellar development and that dysfunction in this pathway may be involved with medulloblastoma pathogenesis. In this context, a new molecular subgroup has been suggested based on the importance of the association between CXCR4 overexpression and sonic hedgehog subgroup. Treatment using CXCR4 antagonists showed significant results, evidencing the important role and possible therapeutic capacity of CXCR4 in MB. This review summarizes studies on MB cell biology, focusing on a chemokine-receptor axis, CXCL12/CXCR4, that may have implications for treatment strategies once it can improve life expectancy and reduce neurocognitive sequelae of patients with this neoplasia.Tumors originate from cells with dysregulation on normal growth mechanism control, caused by genetic mutations. 1 Studies have demonstrated that the tumor microenvironment is constituted not only by tumor cells, but also of extracellular matrix, fibroblasts, endothelial cells and immune cells that could influence tumor progression. 2,3 One chemokine that has been acquiring relevance in cancer is CXCL12, whose receptor CXCR4 is overexpressed in at least 20 different human cancers, including breast cancer, ovarian cancer, melanoma and prostate cancer. 4 Besides their critical role in tumor cell growth, 5 survival and angiogenesis in multiple cancers, 6 this chemokine receptor has been described as an important homing and metastatic mediator of secondary growth in organs that produce CXCL12, such as liver, 7 lung and bone marrow. 8 However, the contribution of CXCR4/CXCL12 axis in organ-specific dissemination and tumor growth has been strongly debated. [9][10][11] Studies have shown that CXCR4, a molecule strongly expressed in proliferating granule neuron precursors (GNP) that are cell types associated with medulloblastoma (MB), 12 is also involved with sonic hedgehog (SHH) pathway, 13 as well as its ligand, that significantly enhances SHH-induced cell proliferation. 14,15 CXCR4 is predominantly expressed in tumor areas, while CXCL12 is expressed mainly in the endothelium of tumor associated blood vessels. 16,17 It has also been described another receptor for the chemokine CXCL12, the CXCR7, however, it seems to play no role in this tumor. 15 CXCL12 and CXCR4 are expressed in several brain tumors, including MB and the expression level of this receptor appears to have prognostic significance. 16,18,19 Positive CXCR4 expression was identified in nine of ten samples of MB tumors, in contrast to little or no staining in normal cerebellum counterparts. 16 Studies als...

Wilms tumor is the most common kidney malignancy in children, especially in children aged less than 6 years. Although therapeutic approach has reached successful rates, there is still room for improvement. Considering the tumor microenvironment, cytokines represent important elements of interaction and communication between tumor cells, stroma, and immune cells. In this regard, the transforming growth factor beta (TGF-β) family members play significant functions in physiological and pathological conditions, particularly in cancer. By regulating cell growth, death, and immortalization, TGF-β signaling pathways exert tumor suppressor effects in normal and early tumor cells. Thus, it is not surprising that a high number of human tumors arise due to alterations in genes coding for various TGF-β signaling components. Understanding the ambiguous role of TGF-β in human cancer is of paramount importance for the development of new therapeutic strategies to specifically block the metastatic signaling pathway of TGF-β without affecting its tumor suppressive effect. In this context, this review attempt to summarize the involvement of TGF-β in Wilms tumor.

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: −0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation.