Complement C5a/C5aR Pathway Participates In The Pathogenesis Of Colon Cancer

Colon caner is one of the most malignant tumor in the worldwide,however,little is konwn about its mechanism.FGL2,a novel prothrombinase,which played procoagulant activity and immunomodulatory activity through the regulation of maturation and proliferation of immune cells,participate in the pathogenesis of many inflammation diseases,howerver,little is known about its potential role in cancer.Complement system is an important part of the innate immune defense and is important for the cellular integrity tissue homeostasis and modifying the adaptive immune response.The complement system can be activated by three ways: classic,alternative and Lectin pathway.The activated complement system can eliminate the invaders and protect our body.This system can also modify self-cells such as apoptotic particles and cellular debris but also can regulate the cell circle by its ligands and receptors.As we know,complement system participate in the pathogenesis of many diseases,however,little is known about its potential mechanism in the cancer.In our study,we notice that high level expression of FGL2 and the activiation of complement system in the colon cancer patients.we hypothesise that they maybe have some kind of connection in colon canecer.In this research,we study the role of C5a-C5 aRpathway in colon cancer and to investigate the regulatory mechanism of C5a-C5 aR pathway in FGL2 expression.Fifteencolon cancer patientswere recruited.Immunohistochemical staining was used to assess the expression of complement activation fragments C5b-9,activated C3,C5aRandFGL2 deposition in colon cancer tissue to verify the complement activation.Western blot was used to detect the extent of phosphorylation of P38 in MAPK signaling pathway and FGL2 expression in colon cancer tissue to clarify the interaction of C5a-C5 aR pathway and FGL2 expression.We get the followed results:The activation fragments C5b-9,activated C3 and C5 aR got higher expression in colon cancer tissue compared with the paratumor.Furthermore,the expression of FGL2 in colon cancer tissue was higher than that in paratumor..Moreover,the MAPK signaling pathway wasalso comprehensively activated in colon cancer tissuesas compared to paratumor.C5 a could promote the extent of phosphorylation of P38 in MAPK signaling pathway and FGL2 expression in Raw264.7.However,C5 aR antagonist could attenuate the expression.Based above all,we can make a conclusion that C5a-C5 aR signaling pathway plays a significant role in the development of colon cancer via regulation of FGL2 expression.