Preliminary Study Of The Role Of B7-H3in Prostate Cancer Bone Metastases

ObjectProstate cancer (PCa) is one of the most common malignant tumors in malepatients. Distant metastases are the major causes of death in the patients with prostatecancer. The exact mechanism of metastase is unclear so far. A large number of studieshave been done, which found the expression of B7-H3in prostate cancer was closelyassociated with the tumor metastasis. B7-H3was found as one of the B7costimulatorymolecules superfamily members by Chapoval. Later, some researches showed thatB7-H3can mediate cell-cell and cell-extracellular matrix protein adhesion, the adhesionfunction of B7-H3provides new clues of the molecules in tumor invasion andmetastasis. This study aimed to explore the role of B7-H3in prostate cancer bonemetastasis, and lay the foundation for the study of B7-H3in tumor metastasismechanism.MethodThis study consists of three parts:(1) The B7-H3over expression vector was transfected into the prostate cancer cellLNCap to get the B7-H3/LNCap with stable over-expression of B7-H3. Then weidentified the transfected cell by the real time PCR, reverse transcription PCR (RT-PCR),flow cytometry (FCM).(2) Cell adhesion assays were used to detect the cell adhesion capability; thewound scrape assays were used to detect the cell migration ability; transwell invasionassays were used to detect the cell invasiveness; apoptosis assays were used to detectthe cells resistance to the adverse environment; enzyme-linked immunosorbent assay(ELISA) was used to detect the MMP-9secretion in the cell supernatant.(3) Some prostate cancer tissue specimens were examined to detect the expressionof B7-H3by Immunohistochemistry (IHC), and some tests in animal models were done. Result(1) On the levels of mRNA and protein, the B7-H3expressions weresignificantantly higher in the transfected prostate cancer cell B7-H3/LNCap than in theuntransfected group detected by real-time PCR, RT-PCR and FCM.(2) By comparing the results of the transfected and untransfected cells, we foundthat the abilities of B7-H3/LNCap in cell adhesion, migration, invasion andanti-apoptotic were significantly more than the untransfected group LNCap. Theexpression of MMP-9in the transfected cell’s supernatant was also significantly higherthan the untransfected group.(3) The expression of B7-H3in prostate cancer was significantly higher than thenormal group by Immunohistochemistry. In animal models, the tumor size ofB7-H3/LNCap group was bigger than that the LNCap group.ConclusionWe successfully construct the prostate cancer cell B7-H3/LNCap with theoverexpression of B7-H3. The overexpression of B7-H3in prostate cancer can improvecancer cell’s adhesion, migration, invasion and anti-apoptotic abilities, and also promotethe secretion of MMP-9. The expressions of B7-H3in prostate cancer tissues wereabnormaly high. B7-H3can suppress the tumor immunity and facilitate cancerprogression.