The Role Of CXCL12 And CXCL14 In Inflammatory Infiltration Of Liver Occurred In Decorin Deficiency Microenvironment Induced Colorectal Cancer

Colorectal cancer(CRC)is one of the most common digestive system tumors.Most patients with colorectal cancer have metastasized when diagnosed,and the liver is the main site of colorectal cancer metastasis.Before colorectal cancer metastasizes to the liver,the microenvironment of the liver changes accordingly.For example,inflammation and infiltration of the liver.Decorin(DCN)is a small molecule proteoglycan rich in leucine.Early laboratory studies have found that DCN plays an important role in the occurrence and metastasis of colorectal cancer.The purpose of this study was to investigate the effect of the metastasis of colorectal cancer on the liver in the absence of DCN and the possible molecular mechanism.The research results are as follows(1)After induction of AOM combined with DSS,inflammatory infiltration of liver in mice with DCN-deficient colorectal cancer occurred.Using azoxymethane(AOM)combined with Dextran sodium sulfate(D SS)to induce wild-type and DCN knockout mice to establish a mouse colorectal cancer model,collected at 12 weeks and 21 weeks,respectively Tissue samples were stained with HE sections and found that compared with 12-week mouse liver tissues,21-week DCN gene knockout mice liver cells showed significant inflammatory infiltration.(2)Treatment of colorectal cancer cells with recombinant DCN protein can regulate the expression of chemokines CXCL12,CXCL14 and downstream signaling pathway molecules.In order to further explore the molecular mechanism of colorectal cancer-hepatic inflammatory invasion caused by the absence of DCN,the optimal concentration of exogenous DCN recombinant protein for colorectal cancer cell SW480 was 5 mg / L.After treating SW480 cells at this concentration for 48 h,the expression of chemokine CXC subfamily(CXC)CXCL1 to CXCL17(except CXCL15)was detected by quantitative real-time PCR(q PCR)method: with the control group In contrast,the expression of CXCL12 with the addition of exogenous DCN recombinant protein was significantly reduced,and the expression of CXCL14 was increased.Further detection of the expression of downstream signaling molecules of CXCL12 revealed that the expression levels of p38 and P-p38 were reduced after the addition of exogenous DCN recombinant protein,and the expression of VEGF-A also decreased.The above results indicate that DCN can affect CXCL12 and CXCL14 in SW480 and inhibit the expression of p38 and VEGF-A.(3)The chemokines CXCL12,CXCL14 and the activation of downstream signaling pathways are involved in DCN deficiency-induced liver inflammatory infiltration in colorectal cancer model mice.Collected 21-week wild-type and DCN knockout mouse colorectal tumor tissues.Western blot results showed that DCN deletion can lead to increased expression of CXCL12,p38,P-p38,VEGF-A in the colorectal cancer tumor microenvironment The decreased expression is consistent with the results of the cell-level studies.In order to further study the inflammatory infiltration in the liver of model mice,we further examined the expression of CXCL12 and VEGF-A in the liver of model mice.The results showed that in the liver of DCN knockout mice: CXCL12 expression increased,and downstream P-p38 and VEGF-A expression increased,indicating that the abnormal expression of CXCL12 and VEGF-A in colorectal cancer tumor microenvironment The inflammatory infiltration of the liver is closely related.The above results indicate that DCN knockout in mouse colorectal tumors can reduce the expression of CXCL14,promote the expression of CXCL12,and activate the p38 signaling pathway in colorectal tumors,resulting in an increase in VEGF-A.The high expression of VEGF-A and CXCL12 in colorectal tumors changes the microenvironment of colorectal cancer tumors,which in turn promotes the increased expression of CXCL12 in the liver,promotes the secretion of VEGF-A by the liver,and changes the liver microenvironment,thus making the DCN knockout type small Inflammation of the rat liver occurred.In summary,the degree of inflammatory infiltration in the liver of DCN-deficient colorectal cancer mice increases with the prolonged modeling period.In the mechanism study,CXCL12 and XCL14 in the DCN-deficient microenvironment may be related to rectal cancer-liver inflammatory invasion.This liver inflammatory infiltration creates favorable conditions for future liver metastasis of colorectal cancer,indicating that DCN may have the potential to inhibit liver metastasis of colorectal cancer.This study also provides a theory for DCN to become a potential biological agent for the treatment of colorectal cancer liver metastasis basis.