Low Doses of PFOA Promote Prostate and Breast Cancer Cells Growth through Different Pathways

Endocrine Disrupting Compounds (EDCs) are found in everyday products. Widely distributed throughout the environment, persistent organic pollutants (POPs) are a specific class of EDCs that can accumulate in adipose tissue. Many of them induce adverse effects on human health—such as obesity, fertility disorders and cancers—by perturbing hormone effects. We previously identified many compounds with EDC activity in the circulation of obese patients who underwent bariatric surgery. Herein, we analyzed the effects of four of them (aldrin, BDE28, PFOA and PCB153) on two cancer cell lines of hormone-sensitive organs (prostate and breast). Each cell line was exposed to serial dilutions of EDCs from 10−6 M to 10−12 M; cytotoxicity and proliferation were monitored using the IncuCyte® technology. We showed that none of these EDCs induce cytotoxicity and that PFOA and PCB153, only at very low doses (10−12 M), increase the proliferation of DU145 (prostate cancer) and MCF7 (breast cancer) cells, while the same effects are observed with high concentrations (10−6 M) for aldrin or BDE28. Regarding the mechanistic aspects, PFOA uses two different signaling pathways between the two lines (the Akt/mTORC1 and PlexinD1 in MCF7 and DU145, respectively). Thus, our study demonstrates that even at picomolar (10−12 M) concentrations PFOA and PCB153 increase the proliferation of prostate and breast cancer cell lines and can be considered possible carcinogens

Epidemic spread of Pandoraea pulmonicola in a cystic fibrosis center.

International audiencePandoraea spp. are recently discovered bacteria, mainly recovered from cystic fibrosis (CF) patients, but their epidemiology and clinical significance are not well known. We describe an epidemic spread of Pandoraea pulmonicola from 2009 in our CF center, involving 6 out of 243 CF patients. Bacterial identification used amplified ribosomal DNA restriction analysis (ARDRA), MALDI-TOF mass spectrometry (MALDI-TOF MS) and 16S rDNA gene sequencing. The clonal link between strains was assessed with pulsed field gel electrophoresis (PFGE) using XbaI. Clinical data were gathered for all patients. The index case was chronically colonized since 2000. The main hypothesis for this bacterial spread was a droplet cross-transmission, due to preventive measures not being strictly followed. Antibiotic susceptibility testing revealed resistance to beta-lactams, ciprofloxacin and colistin. However, there was susceptibility to trimethoprim-sulfamethoxazole. All patients were chronically colonized with Pseudomonas aeruginosa, and the acquisition of P. pulmonicola resulted in chronic colonization in all patients. Three patients died, and two patients remained clinically stable, whereas one patient had a decline in lung function. This study, which is the first to describe an epidemic spread of P. pulmonicola, notes the potential transmissibility of this bacterial species and the need for infection control measures

Quantitative image based analysis of endocrine disruptor effects on mitochondria morphology-function in prostate cancer cells

International audienceEndocrine Disrupting Compounds (EDC) are found in many everyday products, like food packaging, food preservative or additive, pesticides residues, etc… Widely distributed throughout the environment and bioaccumulable in living organisms, persistent organic pollutants (POPs) are a specific class of EDC that accumulate in fat deposit. Some of them have been recognized as causing adverse effects on human’s health such as diabetes and cancer by mimicking hormone effects on metabolism. Cancer cells display high metabolic flexibility allowing them to grow in various cellular environments and favoring their proliferative and invasive capacities. Mitochondria are key players in this complex interplay as they produce ROS, generate energy and participate in nucleotide synthesis and in glutamine metabolism of cancer cells. Regarding the importance of hormones on prostate cancer risk and outcomes, we are developing multiple parameters in vitro assays conducted in a high-throughput screening format relevant for prostate cancer metabolism and aggressiveness. This screening method includes, inter alia a microscopy based analysis of mitochondria structure and function. We analyzed the effects of five EDCs (Aldrin, BDE28, TCDD, PCB153, PFOA) identified in the plasma of patients on two prostate cancer cell lines, 22RV1 (androgen-responsive) and DU145 (androgen-unresponsive). Each compound was tested in a dose dependent manner to determine its effects on total mitochondrial mass, mitochondrial membrane potential, ROS production, mitochondrial biogenesis and mitophagy. In addition, we performed an image based computational analysis of the mitochondrial network morphology and dynamics. This strategy allows us to extract some quantitative parameters on the mitochondrial network as fragmentation index, compactness, average volume, etc. When combined, morphological and functional parameters allow us to discriminate subtle perturbations of the mitochondrial structure-function induced by POPs in prostate cancer cells. We are confident that this multiparameter analysis strategy could represent a new perspective in identification and characterization of EDC based on their effects on cell metabolism (phenoscore) in order to estimate their potential risk on human health