| Prostate cancer is the most common male malignant tumor and the secondleading fatality male malignancy in many western countries. In recent years, aspopulation aging and improvement of the living conditions, the prostate cancerincidence in China has greatly increased. The main therapy means is to operatetogether with radiotherapy, chemotherapy and endocrine therapy. The means hasimproved the five years' survival greatly. However, some patients of advanced stagestill died of the tumor relapse and metastasis.The perineural invasion (PNI) of tumor means the phenomenon that tumor cellshave the ability to embrace nerve fibers and enter lamellar sheath to spread. Prostatecancer always encroach some important nerves, not only bring patients intense pain,but also influence their emiction and generation, depress their living quality. Thisphenomenon closely relates with prostate cancer's local relapse, metastasis andprognosis.In 2001, some researchers found that chemokines may have significant effect ontumor's metastasis to certain directional location. This evoked many researchers'attention and has become a focus in oncology. Chemokine CXCL12 and its receptorCXCR4 were found playing important effect on directional metastasis of melanoma,breast cancer, prostate cancer and synovial sarcoma. The effect and relevantmolecular mechanism of PNI in prostate cancer is still unclear.Object: Study the role of CXCL12-CXCR4, matrix metaloproteinase and nervegrowth factor on prostate cancer PNI and explain related mechanism to provideexperimental support for clinical therapy, decreasing prostate cancer relapse andmetastasis, ameliorating prognosis.Methods: To detect the expression and distribution feature of CXCL12, CXCR4and MMP-2, MMP-9 in human prostate cancer tissue by immunohistochemistrytechnique. Observe the influence of exogenous CXCL12 and AMD3100 (specific antagonist of CXCR4) on PC3 cells' invasive ability by Transwell experiment.Establish animal-transplanted prostate cancer model, then detect the influence ofexogenous CXCL12 and AMD3100 on nerves growth around tumor and theexpression of CXCL12, CXCR4, MMP-2, MMP-9, NGF in tumor byimmunihistochemistry staining. Analyze the results and research relevant molecularmechanism of CXCL12-CXCR4 on prostate cancer PNI.Results: the positive expression rate of CXCL12, CXCR4 and MMP-2, MMP-9in human prostate cancer tissue were all higher than that of prostatic hyperplasia(p＜0.05). In Transwell experiment, exogenous CXCL12 greatly provoted the PC3cells' invasion, while AMD3100 greatly inhibited PC3 cells' invasive ability, thedifferences of three groups were statistically significant (P＜0.05). In animal vivoexperiment, the average nerve number around near tumor tissue from more to lesswere specifically CXCL12group, control group, AMD3100 group, the difference ofthree groups were statistically significant (P＜0.05). The average nerve number nearthe tumor tissue of CXCL12 group and control group were statistically more thanthat far from the tumor tissue(P＜0.05). The positive expression rate ofCXCL12, CXCR4, MMP-2, MMP-9 and NGF in three experimental groups from highto low were specifically CXCL12 group, control group and AMD3100 group, thedifferences among them were all statistically significant (P＜0.05).Conclusion: CXCL12 and its receptor CXCR4 are higher expressed in prostatecancer, CXCL12-CXCR4 and MMPs cooperate to enhance the prostate cancer cells'invasive ability, thus to promote PNI. CXCL12-CXCR4 upregulate the expression ofNGF in prostate cancer cells to stimulate nerve growth around tumor tissue andpromote PNI. Besides, our results prove that AMD3100 can effectively inhibit therole of CXCL12-CXCR4 to supress PNI, this may provide experimenal support forclinical implication ofAMD3100.
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