Basic And Clinical Research Of Osteopontin Expression Involved In Tumor Hypoxia Microenvironment In Esophageal Carcinoma

BackgroundEsophageal cancer is a common malignant tumor, the major cause of death is due to the cancer invasion and metastasis. Recent studies showed that the overexpression of osteopontin(OPN) could be an important role to monitor the tumor recurrence and indicate the prognosis of patients. But there was no report of the correlation with tumor microenvironment of hypoxia. gioleObjectiveBy transplantation tumor model to determine the correlation of OPN expression and tumor hypoxia condition, analyze the correlation between esophageal cancer specimens OPN expression levels with tumor hypoxia state by radiation therapy of esophageal cancer xenografts in nude mice joint hypoxic sensitizer(glycodidazolum sodium), analysis the correlation of serum OPN and hypoxia-sensitizing. PsMethodsPart 1.Animal Experiments We developed esophageal cancer xenograft model in nude mice, mice were sacrificed when the tumor diameter was about 1cm. Transplanted tumor specimens, used immunohistochemistry to detect the correlation of tissue OPN and HIF-1α.Part 2.Clinical Research We used immunohistochemistry to detect OPN and HIF-1α in a selection of 68 cases of esophageal cancer patients were collected from the Department of Thoracic Surgery of Shandong Tumor Hospital from November 2011 to December 2012 after surgical specimens, analyse the correlation between the expression of OPN and HIF-1α. Part 3.Hypoxia efficiency research: We established the esophageal cancer xenografts in nude mice, the nude mice were randomly divided into five groups: non-treatment group, irradiation group and irradiation group + CMNa group(tail vein injection of high, medium and low dose CMNa). Taking eye fissure blood before the treatment. The tumors were irradiated 5Gy X-ray every other day to 30 Gy totally, the tumor growth were monitored by measuring the tumor size before every radiation. The serum levels of OPN were measured by enzyme linked immunosorbent assay(ELISA). Analyse the correlation between the serum OPN concentration and tumor growth, and illustrate the role of OPN in sensitizing effect of hypoxia. PfrResultsThe Spearman correlation analysis showed: the OPN expression in primary tumors and HIF-1αof 68 cases of esophageal cancer patients were significantly correlated(p <0.001, r = 0.43). Xenograft tumor OPN and HIF-1αexpression was positively correlated. The serum levels of OPN could predict hypoxia sensitizing effect. PsConclusionsThe result showed that the high expression of osteopontin and HIF-1 were significantly correlated(p <0.05) both in human and xenograft tumor model. The combination of osteopontin and HIF-1α can be used as an independent prognostic predictors. For patients treated with radiotherapy, OPN also can predict the effect of hypoxia sensitization.