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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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(A) Plating human A-172, U-138, LN-229 or LN-18 glioblastoma cells on FN, Matrigel, polystyrene or BSA differentially altered the cellular radiosensitivity. Survival of A-172 cells grown on FN or Matrigel was significantly (P<0.01) improved at doses ⩾4 Gy. In contrast, irradiated U-138, LN-229 or LN-18 cells showed no substratum-dependent alteration of cell survival. Each data point represents the mean ±s.d. of three independent experiments (n=18). (B) The surviving fractions after 2 (SF2) or 6 Gy (SF6) of A-172 and U-138 cells were significantly (P<0.01) reduced after single or combined β1- and β3-integrin depletion using siRNA transfection (see Western blot) as compared to irradiated cells transfected with unspecific Duplex II RNA (DII). Single Duplex II RNA (Unirr. DII) did not significantly reduce the plating efficiency of A-127 and U-138 cells. * P<0.01.
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fig1: (A) Plating human A-172, U-138, LN-229 or LN-18 glioblastoma cells on FN, Matrigel, polystyrene or BSA differentially altered the cellular radiosensitivity. Survival of A-172 cells grown on FN or Matrigel was significantly (P<0.01) improved at doses ⩾4 Gy. In contrast, irradiated U-138, LN-229 or LN-18 cells showed no substratum-dependent alteration of cell survival. Each data point represents the mean ±s.d. of three independent experiments (n=18). (B) The surviving fractions after 2 (SF2) or 6 Gy (SF6) of A-172 and U-138 cells were significantly (P<0.01) reduced after single or combined β1- and β3-integrin depletion using siRNA transfection (see Western blot) as compared to irradiated cells transfected with unspecific Duplex II RNA (DII). Single Duplex II RNA (Unirr. DII) did not significantly reduce the plating efficiency of A-127 and U-138 cells. * P<0.01.

Mentions: The survival of A-172 cells was significantly (P<0.01) improved following radiation doses ≥4 Gy when grown on FN or Matrigel (Figure 1AFigure 1


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)

(A) Plating human A-172, U-138, LN-229 or LN-18 glioblastoma cells on FN, Matrigel, polystyrene or BSA differentially altered the cellular radiosensitivity. Survival of A-172 cells grown on FN or Matrigel was significantly (P<0.01) improved at doses ⩾4 Gy. In contrast, irradiated U-138, LN-229 or LN-18 cells showed no substratum-dependent alteration of cell survival. Each data point represents the mean ±s.d. of three independent experiments (n=18). (B) The surviving fractions after 2 (SF2) or 6 Gy (SF6) of A-172 and U-138 cells were significantly (P<0.01) reduced after single or combined β1- and β3-integrin depletion using siRNA transfection (see Western blot) as compared to irradiated cells transfected with unspecific Duplex II RNA (DII). Single Duplex II RNA (Unirr. DII) did not significantly reduce the plating efficiency of A-127 and U-138 cells. * P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: (A) Plating human A-172, U-138, LN-229 or LN-18 glioblastoma cells on FN, Matrigel, polystyrene or BSA differentially altered the cellular radiosensitivity. Survival of A-172 cells grown on FN or Matrigel was significantly (P<0.01) improved at doses ⩾4 Gy. In contrast, irradiated U-138, LN-229 or LN-18 cells showed no substratum-dependent alteration of cell survival. Each data point represents the mean ±s.d. of three independent experiments (n=18). (B) The surviving fractions after 2 (SF2) or 6 Gy (SF6) of A-172 and U-138 cells were significantly (P<0.01) reduced after single or combined β1- and β3-integrin depletion using siRNA transfection (see Western blot) as compared to irradiated cells transfected with unspecific Duplex II RNA (DII). Single Duplex II RNA (Unirr. DII) did not significantly reduce the plating efficiency of A-127 and U-138 cells. * P<0.01.
Mentions: The survival of A-172 cells was significantly (P<0.01) improved following radiation doses ≥4 Gy when grown on FN or Matrigel (Figure 1AFigure 1

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