Fibronectin Alters Cell Survival and Intracellular Signaling of Confluent A549 Cultures After Irradiation

Abstract

B i o s c i e n c e . N o t f o r d i s t r i b u t i o n .[Cancer Biology & ACKNOWLEDGEMENTSThe authors are indebted to Dr. Eric J. Bernhard for helpful discussions and critically reading the manuscript and Ms. Monika Kraus for excellent technical assistance. Research Paper Fibronectin Alters Cell Survival and Intracellular Signaling of Confluent A549 Cultures after Irradiation ABSTRACTCell-cell and cell-extracellular matrix contacts influence cellular sensitivity to ionizing radiation. To further define the influence of these interactions on tumor cell survival and cell cycle progression after irradiation without or in combination with the phorbol ester phorbol-12-myristate-13-acetate (PMA), the radiation response of p53 wild-type A549 lung cancer cells grown on polystyrene, fibronectin (FN) or BSA was examined. Confluently growing and log-phase A549 cell cultures irradiated on FN showed significantly greater survival compared to cells irradiated on polystyrene or BSA. There was a significantly greater elevation of G 2 /M cells in FN cultures after irradiation compared to other culture conditions. PMA reduced radiation survival on all three substrata and under both log-phase and confluent culture conditions, but had no effect on the elevation of G 2 /M cells in FN cultures. Induction of Chk1 phosphorylation by irradiation was only seen in FN cultures. Chk2 and Cdk1 phosphorylation and Cdc25C expression also differed between FN and polystyrene cultures. Induction of p53 and p21 by irradiation was modulated but not inhibited by PMA, as were changes in cyclin D1 and pRb. Changes in protein expression and phosphorylation of these cell cycle regulatory proteins coincided tightly with accumulation of cells in G 2 /M after irradiation. These findings clearly demonstrate the influence of both intercellular and cell-substratum interactions on the radiation response without or in combination with PMA and differentiate between the cell survival and cell cycle effects of FN attachment.

Cytoprotective activity of elevated static pressure against oxidative stress in normal human fibroblasts

“…Especially cFN have a role of cytoprotection through some experimental evidences that treatment or overexpression of cFN improved cell survival and inhibited apoptosis following irradiation or treatment of DNA damaging agents. On the high presence of cFN, prolonged G2-phase arrest and more activation of cell cycle checkpoint kinase by DNA damaging agents present a prerequisite for an optimized DNA repair and thus improved cell survival 44,45 .…”

Increased β1 Integrin Is Associated with Decreased Survival in Invasive Breast Cancer

“…Strikingly, these effects were also observed in breast cancer xenografts with no toxicity to the host in vivo (8). In addition, h 1 integrins have been shown to mediate resistance to cytotoxic chemotherapy (9,10) and radiation (11,12) in several human cancers, illustrating its potentially multifaceted role as a therapeutic target and predictive factor. h 1 integrin signaling involves several steps, including binding to key extracellular ligands, such as fibronectin and laminin-1.…”

Fibronectin induces cell proliferation and inhibits apoptosis in human bronchial epithelial cells: pro-oncogenic effects mediated by PI3-kinase and NF-κB

“…Fibronectin has been shown to increase the survival of human lung fibroblasts and bronchial epithelial cells (Aoshiba et al, 1997;Cordes and Beinke, 2004); however, the cellular mechanisms responsible for this effect remain unknown. Similarly, fibronectin is also capable of modulating the apoptosis of bronchial epithelial cells (Aoshiba et al, 1997).…”