Mechanism And Significance Of Gliosis Zone In The Adjacent Hypothalamic Nerve Tissue Of Type T ACP

Adamantinomatou craniopharyngioma(ACP)originates from the residual Rathke’s cystic precursor cell.Clinically,according to the membrane structure and the origin of the tumor,it can be divided into type Q,type S and type T.The origin of type T ACP is located on the distal side of the tuberalis of pituitary,grows toward the floor and occupies the space of of the third ventricle.In addition,because there is only a pia mater between type T ACP and nerve tissue,it is easy to involve hypothalamus nerve.At present,surgical resection is the main treatment for ACP,but the operation is very difficult and is easy to destroy nerve tissue.Therefore,it is of great significance to find a safe way of resection.Previous studies have found that there are finger-like tuber structures between the hypothalamus of type T ACP,which is one of the reasons for hypothalamus injury during type T ACP surgery.In addition,we found that there was a layer of gliosis zone between the tumor and the nerve tissue.At present,it is not clear how the formation mechanism of the gliosis zone and weather can be used as the boundary between tumor and hypothalamic nerve tissue,and whether there are some important neuron or axons in it.Astrocytes are the most widespread cells in the central nervous system,which play the role of central nerve cell supported,energy metabolism maintenance,internal immune system,and other functions.During the repair of inflammation and trauma in the central nervous system,the molecular and phenotypic characteristics of astrocytes will change,the soma will be biger,the synapses will increase,and when the injury persists,the synapses overlap to form glia scar.Therefore,the study of the mechanism of astrocyte activation is important to studying the formation of the gilosis zone in craniopharyngioma.Transforming growth factor-β1(TGF-β1)plays a diverse role in cell proliferation and differentiation,wound healing,and control of the immune system,and plays a key role in the pathological process of many diseases(bone disease,fibrosis,and cancer).In addition,TGF-β1 is an important cytokine in inducing epithelial-mesenchymal transformation(EMT),and EMT is an key pathophysiological process in tumor progression and scar formation(fibrosis).In addition,our group previous study also found that TGF-β1 signal was highly expressed in ACP.However,the role and specific mechanism in the microenvironment of craniopharyngioma have not been explained.Based on the above research background and previous research basis,we propose that TGF-β1 plays the following two roles in the occurrence and development of ACP:on the one hand,it can promote ACP to form finger like structure,and on the other hand,it can activate astrocytes to form gliosis belt.The latter is able to provide surgical boundaries separating the tumor from the hypothalamus.Objective:1.To explore the double-edged sword mechanism of TGF-β1 in promoting the progression of ACP tumor and the formation of glial hyperplasia zone.2.To explore whether the glial hyperplasia zone has a binding effect on the growth of the tumor and whether the tumor can be removed safely along the glial hyperplasia zone.Materials and Method:1.Histological examination included hematoxylin-eosin(HE)staining and immunohistochemistry.Marker,reactive astrocytes and TGF-β1 signal pathway were detected2.Cell experiment:ELISA test to determine whether ACP secreted TGFβ1;plate cloning test to verify proliferation;Wound healing test and Transwell migration test to verify migration ability;Transwell invasion test to verify the invasion ability of ACP tumor cells.The model of glial hyperplastic zone was established in vitro to explore its effect on ACP cell migration.3.Western blotting analysis:The specific mechanism of TGF-β1 promoting the progression of ACP and the formation of glial hyperplasia band was analyzed by Western-bloting assay.4.Statistical analysis:SPSS22.0 was used for statistical analysis,and one-way ANOVA was used for those with normal distribution among groups.The difference was statistically significant(P<0.05).Results:1.TGF-β1 secreted by ACP can promote the proliferation,migration and invasion of ACP cells,and promote ACP form finger-like structure.2.There is a finger-like structure adjacent to the hypothalamus in T-type ACP,and a layer of glial hyperplasia zone dominated by reactive astrocytes is formed around it.3.TGF-β1 can further promote the transformation of astrocytes to activation,and promote the proliferation and migration of reactive astrocytes to form glial hyperplasia zone.4.The model of glial hyperplasia zone in vitro confirmed that it could inhibit the migration of ACP cells,and there was no important nerve tissue in it,which provided the pathological basis for safe total resection of tumor along the glial hyperplasia zone during operation.Conclusion:TGF-β1,secreted by ACP cells,have tow way to influence the development of ACP:one hand,it can increases the proliferation and migration of ACP cells and promotes the formation of tenon-like structure of ACP.The other hand it can promote the proliferation of reactive astrocytes and migrates around the tumor to form a layer of glial hyperplasia band that restricts the growth of tumor.These two effects may be realized through the TGFβRII/pSMAD2/3/SMAD4 signal pathway.