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Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines.

Cordes N, Hansmeier B, Beinke C, Meineke V, van Beuningen D - Br. J. Cancer (2003)

Bottom Line: In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue.Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA.This integrin induction caused improved cell adhesion to FN or Matrigel.

View Article: PubMed Central - PubMed

Affiliation: Institute of Radiobiology, German Armed Forces, Neuherbergstrasse 11, 80937 Munich, Germany. nils_cordes@web.de

ABSTRACT
Effects of ionising radiation on extracellular matrix (ECM)-modulated cell survival and on adhesion and invasion are not well understood. In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue. To examine these effects in more depth, four human glioblastoma cell lines (A-172, U-138, LN-229 and LN-18) were irradiated on fibronectin (FN), Matrigel, BSA or polystyrene. Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA. Irradiation induced a dose-dependent increase in functional beta 1- and beta 3-integrins in all four glioma cell lines. This integrin induction caused improved cell adhesion to FN or Matrigel. In contrast to U-138, LN-229 and LN-18 cells, irradiation strongly impaired A-172 cell invasion. Invasion of all cell lines was inhibited by anti-integrin antibodies, the disintegrin echistatin and the MMP-2/-9 inhibitor III. Additionally, beta 1- and beta 3-integrins modulated basal and radiation-altered gelatinolytic activity of MMP-2. Tested glioblastoma cell lines showed a differential cellular susceptibility to FN or Matrigel which affected the cellular radiosensitivity. Three out of four glioma cell lines demonstrated a combination of a substratum-independent survival after irradiation and an invasive potential which was not affected by irradiation. beta 1- and beta 3-integrins were identified to play a substantial, regulatory role in survival, adhesion, invasion and MMP-2 activity. Detailed insights into radioresistance and invasion processes might offer new therapeutic strategies to enhance cell killing of lethal high-grade astrocytoma.

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Radiation (6 Gy) improved the capability of A-172 and U-138 cells to attach to fibronectin (FN) and Matrigel after 48 h in comparison with BSA or polystyrene (P). To determine functional β1- and β3-integrin engagement in radiation-altered adhesion in these two cell lines, the cells were incubated with specific adhesion-blocking antibodies against β1- (mAb13) or β3-integrins (RUU-PL7F12) or with the disintegrin echistatin. Control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. Columns represent the mean ±s.d. of the optical densities (OD) at 630 nm representing cell adhesion to the different substrates of three independent experiments. Statistical analysis compared adhesion to FN or Matrigel of nonirradiated cells with adhesion to FN or Matrigel of irradiated cells. * P<0.01.
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fig3: Radiation (6 Gy) improved the capability of A-172 and U-138 cells to attach to fibronectin (FN) and Matrigel after 48 h in comparison with BSA or polystyrene (P). To determine functional β1- and β3-integrin engagement in radiation-altered adhesion in these two cell lines, the cells were incubated with specific adhesion-blocking antibodies against β1- (mAb13) or β3-integrins (RUU-PL7F12) or with the disintegrin echistatin. Control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. Columns represent the mean ±s.d. of the optical densities (OD) at 630 nm representing cell adhesion to the different substrates of three independent experiments. Statistical analysis compared adhesion to FN or Matrigel of nonirradiated cells with adhesion to FN or Matrigel of irradiated cells. * P<0.01.

Mentions: Attachment of nonirradiated A-172 and U-138 cells to FN or Matrigel was several fold greater than attachment to polystyrene or BSA (Figure 3Figure 3


Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines.

Cordes N, Hansmeier B, Beinke C, Meineke V, van Beuningen D - Br. J. Cancer (2003)

Radiation (6 Gy) improved the capability of A-172 and U-138 cells to attach to fibronectin (FN) and Matrigel after 48 h in comparison with BSA or polystyrene (P). To determine functional β1- and β3-integrin engagement in radiation-altered adhesion in these two cell lines, the cells were incubated with specific adhesion-blocking antibodies against β1- (mAb13) or β3-integrins (RUU-PL7F12) or with the disintegrin echistatin. Control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. Columns represent the mean ±s.d. of the optical densities (OD) at 630 nm representing cell adhesion to the different substrates of three independent experiments. Statistical analysis compared adhesion to FN or Matrigel of nonirradiated cells with adhesion to FN or Matrigel of irradiated cells. * P<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376852&req=5

fig3: Radiation (6 Gy) improved the capability of A-172 and U-138 cells to attach to fibronectin (FN) and Matrigel after 48 h in comparison with BSA or polystyrene (P). To determine functional β1- and β3-integrin engagement in radiation-altered adhesion in these two cell lines, the cells were incubated with specific adhesion-blocking antibodies against β1- (mAb13) or β3-integrins (RUU-PL7F12) or with the disintegrin echistatin. Control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. Columns represent the mean ±s.d. of the optical densities (OD) at 630 nm representing cell adhesion to the different substrates of three independent experiments. Statistical analysis compared adhesion to FN or Matrigel of nonirradiated cells with adhesion to FN or Matrigel of irradiated cells. * P<0.01.
Mentions: Attachment of nonirradiated A-172 and U-138 cells to FN or Matrigel was several fold greater than attachment to polystyrene or BSA (Figure 3Figure 3

Bottom Line: In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue.Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA.This integrin induction caused improved cell adhesion to FN or Matrigel.

View Article: PubMed Central - PubMed

Affiliation: Institute of Radiobiology, German Armed Forces, Neuherbergstrasse 11, 80937 Munich, Germany. nils_cordes@web.de

ABSTRACT
Effects of ionising radiation on extracellular matrix (ECM)-modulated cell survival and on adhesion and invasion are not well understood. In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue. To examine these effects in more depth, four human glioblastoma cell lines (A-172, U-138, LN-229 and LN-18) were irradiated on fibronectin (FN), Matrigel, BSA or polystyrene. Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA. Irradiation induced a dose-dependent increase in functional beta 1- and beta 3-integrins in all four glioma cell lines. This integrin induction caused improved cell adhesion to FN or Matrigel. In contrast to U-138, LN-229 and LN-18 cells, irradiation strongly impaired A-172 cell invasion. Invasion of all cell lines was inhibited by anti-integrin antibodies, the disintegrin echistatin and the MMP-2/-9 inhibitor III. Additionally, beta 1- and beta 3-integrins modulated basal and radiation-altered gelatinolytic activity of MMP-2. Tested glioblastoma cell lines showed a differential cellular susceptibility to FN or Matrigel which affected the cellular radiosensitivity. Three out of four glioma cell lines demonstrated a combination of a substratum-independent survival after irradiation and an invasive potential which was not affected by irradiation. beta 1- and beta 3-integrins were identified to play a substantial, regulatory role in survival, adhesion, invasion and MMP-2 activity. Detailed insights into radioresistance and invasion processes might offer new therapeutic strategies to enhance cell killing of lethal high-grade astrocytoma.

Show MeSH
Related in: MedlinePlus