CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models.

BACKGROUND: CD147 (basigin, EMMPRIN) is a multifunctional, highly conserved glycoprotein enriched in pancreatic ductal adenocarcinomas (PDACs) which is associated with poor prognosis in many malignancies. The role of CD147 in pancreatic cancer, however, remains elusive. METHODS AND RESULTS: Silencing of CD147 by RNA interference (RNAi) reduced the proliferation rate of MiaPaCa2 and Panc1 cells. CD147 is required for the function and expression of the monocarboxylate transporters MCT1 and MCT4 that are expressed in human PDAC cells as demonstrated by real-time reverse transcription-PCR (RT-PCR) as well as immunohistology. MCT1 and MCT4 are the natural transporters of lactate, and MiaPaCa2 cells exhibited a high rate of lactate production, which is characteristic for the Warburg effect, an early hallmark of cancer that confers a significant growth advantage. Further induction of lactate production by sodium azide in MiaPaCa2 cells increased MCT1 as well as MCT4 expression. CD147 silencing inhibited the expression and function of MCT1 and MCT4 and resulted in an increased intracellular lactate concentration. Addition of exogenous lactate inhibited cancer cell growth in a dose-dependent fashion. In vivo, knock-down of CD147 in MiaPaCa2 cells by inducible short hairpin RNA (shRNA)-mediated CD147 silencing reduced invasiveness through the chorioallantoic membrane of chick embryos (CAM assay) and inhibited tumourigenicity in a xenograft model in nude mice. CONCLUSION: The function of CD147 as an ancillary protein that is required to sustain the expression and function of MCT1 and MCT4 is involved in the association of CD147 expression with the malignant potential of pancreatic cancer cells exhibiting the Warburg effect.

[Roentgenologic diagnosis of coronary vessel calcinosis in patients over 65 years of age]. / Röntgenologisch nachweisbare Herzkranzgefäss-Verkalkkngen bei über 65jährigen.

215 out-patients aged between 65 and 88 years (average age 70.3 years) were examined radiologically for coronary calcification. In 62.5% of the cases positive results were obtained with a prevalence of men over women. From the 134 patients with coronary calcification 81.5% had a pathological ECG and 32% of these showed evidence of transmural infarction. The combination of coronary calcification and chronic arterial hypertension was found in 68.5% of the patients. In our opinion radioscopy of the heart for the detection of coronary calcification is of particular diagnostic value, on account of its safety and simplicity, especially with elderly patients; all the more so since the otherwise usual diagnostic techniques such as ergometry and selective coronary angiography can, for reasons of age, only be performed in certain cases.

Comparative immunophenotyping of monocytes from symptomatic and asymptomatic atopic individuals.

BACKGROUND: Allergy has at least two components - a genetic predisposition referred to as atopy and the progress from an atopic state to clinically apparent disease. Peripheral blood monocytes are circulating myeloid precursors of antigen-presenting cells. The expression of cell surface proteins on monocytes may therefore witness the disease status and affect the development of allergic disease. METHODS: Monocytes were isolated from atopic individuals with seasonal allergic rhinitis (n = 10), from atopic individuals sensitized to aeroallergens but without any signs of acute disease (n = 11), and from healthy nonatopic donors (n = 21). Detailed comparative phenotypic analysis of CD14(+) and FcepsilonRI(+)CD14(+) monocytes was performed by flow cytometry. RESULTS: CD14(+) monocytes from symptomatic atopic donors showed a significant increase in the cell surface intensity of the integrin adhesion molecule CD11c over monocytes from asymptomatic atopic and nonatopic donors. Asymptomatic atopic individuals showed significantly enhanced expression of FcepsilonRI on the CD14(high)CD16(dim) monocyte subset compared with this subset from symptomatic atopic and nonatopic donors. CONCLUSION: The increase in monocyte surface intensity of the adhesion molecule CD11c may be involved in the manifestation of allergic disease. FcepsilonRI on CD14(high)CD16(dim) monocytes of asymptomatic atopic donors may be of functional importance for the maintenance of clinical unresponsiveness toward allergens.