Cancer-associated fibroblasts contribute to cancer metastasis and apoptosis resistance in human ovarian cancer via paracrine SDF-1a

Background Cancer-associated fibroblasts (CAFs), one of the main members of stromal cells in tumor microenvironment are proposed to play a central role in promoting tumor metastasis. It is unclear whether and how CAFs mediates tumor metastasis or chemoresistance in human ovarian cancer. Methods CAFs were extracted from human ovarian cancer tissues (OCs) of patients with different kinds of histological types. Results We found that CAFs showed more aggressive potency than those tumor cells, both of which were isolated from the same ovarian cancer specimen. Moreover, when co-cultured with CAFs, cell migration abilities of ovarian cancer cells (SKOV3, OVCAR3 and HEY) were significantly increased. Next, we preliminarily detected a higher CAFs density in sections of metastatic lesions than those in primary tumor site of primary OCs clinically. However, no significant difference of stromal derived factors-1α (SDF-1α) production from CAFs was found between primary and metastatic lesions. Additionally, in contrast with tumor cells, CAFs exhibited obvious apoptosis resistance when treated with cisplatin. Furthermore, we found that cisplatin-induced cytotoxicity and apoptosis were significantly inhibited by co-cultured with recombinant human SDF-1α in SKOV3 in a time and dose-dependent manner, and this effect was suppressed by the CXCR4 antagonist AMD3100. Conclusions CAFs might be involved in the malignant metastasis in human ovarian cancer through promoting cell migration in tumor cells. And their resistance to cytotoxic agents might be mediated by paracrine SDF-1α/CXCR4 signaling in ovarian cancer (AU)

Cancer-associated fibroblasts contribute to cancer metastasis and apoptosis resistance in human ovarian cancer via paracrine SDF-1α.

BACKGROUND: Cancer-associated fibroblasts (CAFs), one of the main members of stromal cells in tumor microenvironment are proposed to play a central role in promoting tumor metastasis. It is unclear whether and how CAFs mediates tumor metastasis or chemoresistance in human ovarian cancer. METHODS: CAFs were extracted from human ovarian cancer tissues (OCs) of patients with different kinds of histological types. RESULTS: We found that CAFs showed more aggressive potency than those tumor cells, both of which were isolated from the same ovarian cancer specimen. Moreover, when co-cultured with CAFs, cell migration abilities of ovarian cancer cells (SKOV3, OVCAR3 and HEY) were significantly increased. Next, we preliminarily detected a higher CAFs density in sections of metastatic lesions than those in primary tumor site of primary OCs clinically. However, no significant difference of stromal derived factors-1α (SDF-1α) production from CAFs was found between primary and metastatic lesions. Additionally, in contrast with tumor cells, CAFs exhibited obvious apoptosis resistance when treated with cisplatin. Furthermore, we found that cisplatin-induced cytotoxicity and apoptosis were significantly inhibited by co-cultured with recombinant human SDF-1α in SKOV3 in a time and dose-dependent manner, and this effect was suppressed by the CXCR4 antagonist AMD3100. CONCLUSIONS: CAFs might be involved in the malignant metastasis in human ovarian cancer through promoting cell migration in tumor cells. And their resistance to cytotoxic agents might be mediated by paracrine SDF-1α/CXCR4 signaling in ovarian cancer.

[The relationship between the levels and variability of blood glucose and the prognosis of massive cerebral infarction].

OBJECTIVE: To investigate the relationship between the levels and variability of blood glucose and the prognosis of massive cerebral infarction. METHODS: A retrospective study involving 72 massive cerebral infarction patients without diabetes mellitus admitted to Taizhou Enze Medical Centre Luqiao Hospital from January 2012 to June 2013 was conducted. The mean blood glucose level (GluAve), standard deviation of blood glucose level (GluSD), and coefficient of variation of blood glucose level (GluCV) during the first 72 hours were monitored. Complications such as cerebrocardiac syndrome, pulmonary infection, stress ulcer bleeding, urinary system infection, decubitus sore, electrolyte disturbances, and epileptic seizures were also recorded. According to the 28-day outcome after admission, patients were divided into survivor group (n=60) and non-survivor group (n=12). The values of GluAve, GluSD and GluCV were compared between the two groups. The patients were again divided into three groups based on the level of GluAve (<7.8, 7.8-11.1, >11.1 mmol/L). Finally, patients were divided into four groups based on the level of GluCV (<15%, 15%-30%, 30%-50%, >50%). Acute physiology and chronic health evaluation II (APACHEII) score, mortality, and complications were compared among groups. RESULTS: The levels of GluAve, GluSD and GluCV in non-survivor group were significantly higher than those in survivor group [GluAve: 17.91 ± 5.33 mmol/L vs. 12.41 ± 3.12 mmol/L, t=3.145, P=0.002; GluSD:2.87 ± 1.96 mmol/L vs. 1.83 ± 1.08 mmol/L, t=2.611, P=0.017; GluCV: (27.56 ± 14.73)% vs. (20.12±10.97)%, t=2.020, P=0.043]. With the gradual increase of GluAve level, the mortality and total complication rate were elevated significantly [28-day mortality: 5.00% (1/20), 13.89% (5/36), 37.50% (6/16), χ²=7.16, P=0.028; total complication rate: 35.00% (7/20), 55.56% (20/36), 93.75% (15/16), χ²=12.85, P=0.002]. But there was no significant difference in APACHEII score (9.80 ± 4.17, 12.11 ± 5.81, 13.69 ± 6.57, F=2.241, P=0.114) and stress ulcer incidence rate [5.00% (1/20), 11.11% (4/36), 31.25% (5/16), χ²=5.59, P=0.061]. With the gradual increase of GluCV level, APACHEII score, 28-day mortality, the incidence of various complications, and total complication rate were all raised significantly [APACHEII score: 7.00 ± 1.56, 10.08 ± 1.88, 13.14 ± 5.76, 16.76 ± 7.17, F=12.486, P=0.000; mortality: 0 (0/15), 8.70% (2/23), 23.81% (5/21), 38.46% (5/13), χ²=9.27, P=0.026; total complication rate: 40.00% (6/15), 47.83% (11/23), 57.14% (12/21), 100.00% (13/13), χ²=12.42, P=0.006]. CONCLUSIONS: Both the GluAve level and GluCV level are significantly correlated with the outcome of patients suffering from massive cerebral infarction. The change in GluCV level seems to be more sensitive in predicting the prognosis of massive cerebral infarction than GluAve.