Ionizing radiation induces up-regulation of functional β 1-integrin in human lung tumour cell lines in vitro

Cordes, Nils; Blaese, Marcel A.; Meineke, Viktor; Beuningen, D. van

doi:10.1080/09553000110117340

Cited by 79 publications

(73 citation statements)

References 35 publications

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“…For instance, x-ray irradiation increases expression of functional integrins β1 and β3 in glioma cell lines in a dose-dependent manner [8]. In lung adenocarcinoma A549 and SKMES1 cells, x-ray irradiation also induces expression of functional integrin β1 [9]. Furthermore, a signal through the cytoplasmic domains of integrin β1 contributes to cell survival after irradiation [10].…”

Section: Introductionmentioning

confidence: 99%

Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Ishihara

Haga

Yasuda

et al. 2010

Biochemical and Biophysical Research Communications

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Radiotherapy is one of the effective therapies used for treating various malignant tumors.However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin β1 activity-dependent migratory pattern.In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin β1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin β1-dependent phenotype, and integrin β1 might be a potentially effective therapeutic target in combination with radiotherapy.

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Section: Introductionmentioning

confidence: 99%

Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Ishihara

Haga

Yasuda

et al. 2010

Biochemical and Biophysical Research Communications

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“…In accordance with previously reported observations on cell adhesion-mediated radioresistance of exponentially growing A549 cells, confluently growing A549 cells showed a significantly improved survival after irradiation on FN compared to cells irradiated on polystyrene or BSA. 10,13 Although overall survival was reduced by PMA treatment, FN was able to strongly mediate a radioprotective effect in PMAtreated cells. The PMA concentration used in these experiments was not toxic but had sensitizing effects in both confluently growing as well as log-phase cell cultures.…”

Section: Discussionmentioning

confidence: 99%

“…7,8,[10][11][12][13] Cell communication systems are highly developed in most tissues. Their metabolic cooperation is well documented and usually results in enhanced cell survival in normal and tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] The same communication networks account for an increased resistance to ionizing radiation (IR) in a variety of transformed and normal cell lines in vitro. [7][8][9][10][11][12][13] Whereas cell-ECM interactions are mainly mediated through the integrin receptor family, cell-cell interactions are transduced by an exchange of soluble signaling molecules through gap juntions and by specific cell adhesion molecules (CAMs) such as certain members of the integrin family, the immunoglobulin superfamily and E-cadherin. 1,[14][15][16] To what extent cell-matrix and cell-cell contacts contribute to increased survival during the cellular response to IR as well as the molecular mechanisms involved is unclear to date.…”

Section: Introductionmentioning

confidence: 99%

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

Cordes¹,

Beinke²

2004

Cancer Biology & Therapy

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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.

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“…Activation of the integrin pathway contributes to tumor radioresistance, and downstream focal adhesion kinase (FAK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling have been linked to decreased radiation responsiveness in various malignant tumors, including head and neck cancer, pancreatic cancer, breast cancer, nasopharyngeal carcinoma, and glioblastoma (12)(13)(14)(15)(16)(17). In human lung cancer cells, the upregulation of functional integrin b1 induced by ionizing radiation represents a prerequisite for metastasis (18). FAK knockdown enhanced the radiosensitivity of HNSCC cells, and the downstream molecules of FAK, including paxillin, Akt1, and ERK1/2, were substantially dephosphorylated under FAK depletion (19).…”

Section: Introductionmentioning

confidence: 99%

HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling

Dang³

et al. 2015

Molecular Cancer Therapeutics

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Radiotherapy has played a limited role in the treatment of hepatocellular carcinoma (HCC) due to the risk of tumor radioresistance. A previous study in our laboratory confirmed that CD147 interacts with integrin b1 and plays an important role in modulating the malignant properties of HCC cells. In this study, we further evaluated the role of CD147 in the radioresistance of HCC and as a potential target for improving radiosensitivity. Upon irradiation, the colony formation, apoptosis, cell-cycle distribution, migration, and invasion of SMMC-7721, CD147-knockout SMMC-7721, HepG2, and CD147-knockdown HepG2 cells were determined. A nude mouse xenograft model and a metastatic model of HCC were used to detect the role of CD147 in radioresistance in vivo. Deletion of HAb18G/CD147 significantly enhanced the radiosensitivity of SMMC-7721 and HepG2 cells, and knocking out HAb18G/CD147 in SMMC-7721 cells attenuated irradiation-enhanced migration and invasion. The knockout and antibody blockade of CD147 decreased the tumor growth and metastatic potentials of HCC cells under irradiation. CD147-deleted SMMC-7721 cells showed diminished levels of calpain, cleaved talin, active integrin b1, and decreased p-FAK (Tyr397) and p-Akt (Ser473) levels. FAK and PI3K inhibitors, as well as integrin b1 antibodies, increased the radiation-induced apoptosis of SMMC-7721 cells. Our data provide evidence for CD147 as an important determinant of radioresistance via the regulation of integrin b1 signaling. Inhibition of the HAb18G/CD147 integrin interaction may improve the efficiency of radiosensitivity and provide a potential new approach for HCC therapy.

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Ionizing radiation induces up-regulation of functional β 1-integrin in human lung tumour cell lines in vitro

Cited by 79 publications

References 35 publications

Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

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

HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling

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