Adipocytes take part in a two-way communication with ALL

cells which leads to the secretion of factor(s) that confer resistance to daunorubicin. Adipose tissue may contribute to increased ALL relapse in obese GSK2399872A in vitro patients. O68 Human Lung Fibroblasts Prematurely Senescent after Pexidartinib Exposure to Ionizing Radiation Enhance the Growth of Malignant Epithelial Cells in vitro and in vivo Adamantia Papadopoulou1, Dimitris Kletsas 1 1 Institute of Biology, NCSR “”Demokritos, Ag. Paraskevi, Athens, Greece Cellular senescence is considered to be a potent anticancer mechanism. However, it has been proposed that senescent stroma cells may enhance the growth of adjacent malignant epithelial cells. Exposure of tumours to repeated low doses of γ-irradiation is a common treatment regime in several tissues. However, the effect of this stress to the

neighboring stromal Cytoskeletal Signaling inhibitor cells and the interaction of the latter with cancer cells have not been adequately investigated. In this study, we have exposed confluent cultures of human lung fibroblasts, derived from normal or cancer-associated regions, to repeated subcytotoxic doses of 4 Gy of γ-irradiation. We have found that a single dose immediately activates a DNA damage response, as shown by the activation of the ATM/Chk2/p53/p21WAF1 axis, leading to an intense cell cycle arrest. After a series of doses (total dose approx. 50 Gy), followed by cell subculturing, cellular senescence was accelerated, as shown by morphological alterations, growth arrest, p21WAF1 and p16INK4a upregulation and senescence-associated β galactosidase staining. This process was Idoxuridine found to be p53-dependent. Next, we studied the effect of these prematurely senescent cells on the growth of human malignant lung cell lines (A549 and H1299). Medium conditioned by young and prematurely senescent cells has no major effect on the proliferation of all three cell lines. However, in co-culture studies we

have found that the growth of cancer cells was strongly enhanced when cultured on senescent cells. In addition, in immunocompromised (SCID) mice γ-irradiation-induced senescent cells, similarly to replicative senescent fibroblasts, intensely promoted A549 cells to form tumours; this process was partly dependent on the upregulation of matrix metalloproteases in senescent cells. These findings support the idea that replicative- or stress-induced-senescence may contribute to tumourigenesis. This work has been partly supported by ΚΕΣΥ. O69 Cancer-Associated Fibroblasts Protect Head and Neck Squamous Cell Carcinoma Cells from Cetuximab-Induced Cytotoxicity Ann-Charlotte Johansson 1,2 , Arne Östman2, Karin Roberg1 1 Division of Oto-Rhino-Laryngology, Linköping University Hospital, Linköping, Sweden, 2 Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with 650 000 new cases worldwide every year.