sodium-chlorate and Glioma

The stimulatory input of extracellular matrix (ECM) components has been implicated in the invasive properties of glioma cells. It has been demonstrated that undersulfation of glycosaminoglycans (GAGs) promoted by sodium chlorate (SC) treatment reduces C6 glioma cell proliferation and adhesion to ECM molecules, in-vitro. In the present study, the authors investigated the involvement of GAG undersulfation in glioma cell growth in the brain parenchyma. The in-vitro treatment of C6 cells with SC and subsequent intracerebral inoculation in vehicle containing SC resulted in a reduced proportion of animals bearing glioma and a reduced tumor mass diameter. It also promoted longer animal survival. Intracerebral inoculation of SC-treated C6 cells in vehicle without SC or the SC treatment after intracerebral implantation of untreated C6 cells did not result in any reduction of tumor growth. Alterations in clinical, hematological and behavioral parameters in the open field were observed near the point of death when tumors presented a greater size. The results suggest an important role of GAGs in glioma growth which possibly affects cell proliferation and/or interactions with the normal tissue environment.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Brain Tissue Transplantation; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Chlorates; Disease Progression; Extracellular Matrix; Glioma; Glycosaminoglycans; Herbicides; Male; Neoplasm Invasiveness; Rats; Rats, Wistar; Sulfates; Survival Rate; Treatment Outcome

Proteoglycans are considered to be important molecule in cell-microenvironment interactions. They are overexpressed in neoplastic cells modifying their growth and migration in hosts. In this work we verified that undersulfation of proteoglycans and other sulfated molecules, induced by sodium chlorate treatment, inhibited C6 glioma cells proliferation in a dose-dependent way. This effect was restored by the addition of exogenous heparin. We could not detect significant cell mortality in our culture condition. The treatment also impaired in a dose-dependent manner, C6 cell adhesion to extracellular matrix (ECM) proteins (collagen IV, laminin and fibronectin). In addition, sodium chlorate treatment altered C6 glioma cell morphology, from the fibroblast-like to a more rounded one. This effect was accompanied by increased synthesis of fibronectin and alterations in its extracellular network organization. However, we could not observe modifications on laminin organization and synthesis. The results suggest an important connection between sulfation degree with important tumor functions, such as proliferation and adhesion. We suggest that proteoglycans may modulate the glioma microenvironment network during tumor cell progression and invasion.

Topics: Animals; Cell Adhesion; Cell Differentiation; Cell Division; Chlorates; Extracellular Matrix; Fibronectins; Glioblastoma; Glioma; Laminin; Proteins; Proteoglycans; Rats; Reference Values; Sulfates; Tumor Cells, Cultured