Inflammation has recently been implicated in cancer formation and progression. As tissue transglutaminase (TG2) has been associated with both inflammatory signaling and tumor cell behavior, we propose that TG2 may be an important link inducing interleukin-6 (IL-6)-mediated cancer cell aggressiveness, including cancer stem cell-like characteristics and distant hematogenous metastasis. We evaluated the effect of differential TG2 and IL-6 expression on in vivo distant metastasis of human ovarian cancer cells. IL-6 production in human ovarian cancer cells was dependent on their TG2 expression levels. The size and efficiency of tumor sphere formation were correlated with TG2 expression levels and were dependent on TG2-mediated IL-6 secretion in human ovarian cancer cells. Primary tumor growth and propagation in the peritoneum and distant hematogenous metastasis into the liver and lung were also dependent on TG2 and downstream IL-6 expression levels in human ovarian cancer cells. In this report, we provide evidence that TG2 is an important link in IL-6-mediated tumor cell aggressiveness, and that TG2 and downstream IL-6 could be important mediators of distant hematogenous metastasis of human ovarian cancer cells. Intervention specific to TG2 and/or downstream IL-6 in ovarian cancer cells could provide a promising means to control tumor metastasis.
Axis, Cervical Vertebra* ; Humans* ; Inflammation ; Interleukin-6 ; Liver ; Lung ; Neoplasm Metastasis* ; Ovarian Neoplasms* ; Peritoneum

Objective: This study evaluated the usefulness, as a risk factor of 30-day mortality, in patients residing in nursing-homes (NHs) or long-term care facilities with the diagnosis of pneumonia. Methods: We conducted a retrospective study in a public hospital between January 2017 and December 2017. The subjects included elderly patients residing in NHs and diagnosed with pneumonia in the emergency room. Data on age, gender, comorbidities, laboratory findings, pneumonia severity index score (PSI), and CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and Age 65 or older) were entered into an electronic database. Results: A total of 439 patients were enrolled during the study period. The mean age was 82.1±8.0 years; 195 (44.4%) were men, and 30-day mortality was 21.8%. On multivariate Cox proportional hazard analysis, cerebrovascular accidents (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33-0.87; P=0.012), chronic renal disease (HR, 2.28; 95% CI, 1.11-4.67; P=0.024), malignancy (HR, 1.69; 95% CI, 1.04-2.76; P=0.034), lactate (HR, 1.02; 95% CI, 1.01-1.03; P<0.001), albumin (HR, 0.52; 95% CI, 0.36-0.73; P<0.001), and red cell distribution width (RDW; HR, 1.11; 95% CI, 1.03- 1.19; P=0.007) were independently associated with 30-day mortality. Areas under the curve of PSI, RDW, albumin, lactate, and PSI+RDW+albumin+lactate were 0.690 (95% CI, 0.629-0.751), 0.721 (95% CI, 0.666-0.775), 0.668 (95% CI, 0.607-0.728), 0.661 (95% CI, 0.597-0.726), and 0.801 (95% CI, 0.750-0.852), respectively. Conclusion RDW, albumin, lactate and especially the combination of PSI and these factors appear to be major determinants of 30-day mortality in NH residents with pneumonia.