976

ADGRE5

adhesion G protein-coupled receptor E5;ADGRE5;adhesion G protein-coupled receptor E5

CD97 antigen|CD97 molecule|leukocyte antigen CD97|seven transmembrane helix receptor|seven-span transmembrane protein|seven-transmembrane, heterodimeric receptor associated with inflammation

19p13.12

protein-coding

BACKGROUND: Various evidence show that CD97 plays an important role in tumor differentiation, migration, invasiveness, and metastasis by binding its cellular ligand CD55. CD55 is a complement regulatory protein expressed by cells to protect them from bystander attack by complement, and it has been shown to be an indicator of poor prognostic in several cancers. METHODS: CD97 and CD55 stains were detected in tumor tissues from 71 cases of rectal adenocarcinomas and their corresponding normal colorectal tissues by immunohistochemistry. RESULTS: The expressions of CD97 and CD55 in rectal tumor tissues were significantly higher than those in normal colorectal tissues (P < 0.05, both). The patients with recurrence and/or metastasis had significantly higher expressions of CD97 at tumor cells and CD55 at stroma (67.8% [21/31] and 63.6% [21/33]) at the invasion front than those patients without recurrence and/or metastasis (25.0% [10/40] and 26.3% [10/38]). The expression of CD97 at tumor cell at the invasion front showed modest correlation with that of CD55 in the stroma at the invasion front(r = 0.392, P < 0.01). Univariate analysis revealed that lymph node metastasis (P = 0.001), stages II-IV (P = 0.026), and strong CD97 expression at tumor invasion front (P = 0.002) were shown to have a significant adverse impact on the postoperative survival rate. Moreover, lymph node metastasis (P = 0.037) and strong CD97 expression (P = 0.015) were associated with poor survival in a multivariate analysis. CONCLUSIONS: Elevated expression of CD97 and its ligand CD55 at the invasion front correlate with tumor recurrence and metastasis, and CD95 may be a poor prognostic factor for rectal adenocarcinoma.

CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data we further aimed to investigate the role of CD97 small isoform in gastric cancer progression in vivo by employing the cells with a stable CD97 small isoform knock-down and an orthotopic gastric cancer mouse model. We could demonstrate that the knock down of CD97/EGF1,2,5, led to a significant decrease in the number of cells penetrating the gelatin coated membrane as compared with control cells. In the gastric cancer mouse model, both the hypodermic and the orthotopic yielded tumor masses of the CD97/EGF1,2,5kd group and were significantly smaller than the control. metastatic tumor cell number in early metastatic regional lymph nodes on post-operative day 42 was distinctly decreased in the CD97/EGF1,2,5kd group as compared with the SGC-NS group, and was accompanied with the downregulation of CD44, VEGFR, CD31 and CD97. We concluded in this study that CD97 small isoform not only supported gastric cancer local growth, but also promoted metastatic spread in orthotopically implanted mouse model suggesting involvement of the CD97 small isoform in the preparation of (pre)metastatic niche.