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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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The in-vitro invasion assay indicated that irradiation (6 Gy) is able to inhibit strongly A-172 but not U-138, LN-229 and LN-18 cell invasion into Matrigel. To analyse the dependence of the invasion process on MMP-2 or β1- or β3-integrins, nonirradiated as well as irradiated cells were either incubated with the MMP-2/-9 inhibitor III (MI), anti-β1- (mAb13) and anti-β3-integrin (RUU-PL7F12) antibodies or the β1-/β3-integrin-blocking disintegrin echistatin alone or in combination. Additionally, control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. The data were collected by counting the number of cells per field (four high-powered fields). Columns represent the calculated mean ±s.d. of three independent experiments. Statistical significance was calculated by comparing the rate of invasion after anti-MMP and/or anti-integrin treatment to the rate of invasion of untreated cells. Furthermore, statistics were calculated by comparing the rate of invasion of treated cells after irradiation to the rate of invasion after irradiation alone. nt, no treatment; *P<0.01.
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fig4: The in-vitro invasion assay indicated that irradiation (6 Gy) is able to inhibit strongly A-172 but not U-138, LN-229 and LN-18 cell invasion into Matrigel. To analyse the dependence of the invasion process on MMP-2 or β1- or β3-integrins, nonirradiated as well as irradiated cells were either incubated with the MMP-2/-9 inhibitor III (MI), anti-β1- (mAb13) and anti-β3-integrin (RUU-PL7F12) antibodies or the β1-/β3-integrin-blocking disintegrin echistatin alone or in combination. Additionally, control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. The data were collected by counting the number of cells per field (four high-powered fields). Columns represent the calculated mean ±s.d. of three independent experiments. Statistical significance was calculated by comparing the rate of invasion after anti-MMP and/or anti-integrin treatment to the rate of invasion of untreated cells. Furthermore, statistics were calculated by comparing the rate of invasion of treated cells after irradiation to the rate of invasion after irradiation alone. nt, no treatment; *P<0.01.

Mentions: The basal invasive potential of A-172 and U-138 cells into Matrigel differed by seven-fold (Figure 4Figure 4


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)

The in-vitro invasion assay indicated that irradiation (6 Gy) is able to inhibit strongly A-172 but not U-138, LN-229 and LN-18 cell invasion into Matrigel. To analyse the dependence of the invasion process on MMP-2 or β1- or β3-integrins, nonirradiated as well as irradiated cells were either incubated with the MMP-2/-9 inhibitor III (MI), anti-β1- (mAb13) and anti-β3-integrin (RUU-PL7F12) antibodies or the β1-/β3-integrin-blocking disintegrin echistatin alone or in combination. Additionally, control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. The data were collected by counting the number of cells per field (four high-powered fields). Columns represent the calculated mean ±s.d. of three independent experiments. Statistical significance was calculated by comparing the rate of invasion after anti-MMP and/or anti-integrin treatment to the rate of invasion of untreated cells. Furthermore, statistics were calculated by comparing the rate of invasion of treated cells after irradiation to the rate of invasion after irradiation alone. nt, no treatment; *P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: The in-vitro invasion assay indicated that irradiation (6 Gy) is able to inhibit strongly A-172 but not U-138, LN-229 and LN-18 cell invasion into Matrigel. To analyse the dependence of the invasion process on MMP-2 or β1- or β3-integrins, nonirradiated as well as irradiated cells were either incubated with the MMP-2/-9 inhibitor III (MI), anti-β1- (mAb13) and anti-β3-integrin (RUU-PL7F12) antibodies or the β1-/β3-integrin-blocking disintegrin echistatin alone or in combination. Additionally, control experiments were performed using equivalent concentrations of unspecific anti-mouse IgG2a or IgG1 antibodies. The data were collected by counting the number of cells per field (four high-powered fields). Columns represent the calculated mean ±s.d. of three independent experiments. Statistical significance was calculated by comparing the rate of invasion after anti-MMP and/or anti-integrin treatment to the rate of invasion of untreated cells. Furthermore, statistics were calculated by comparing the rate of invasion of treated cells after irradiation to the rate of invasion after irradiation alone. nt, no treatment; *P<0.01.
Mentions: The basal invasive potential of A-172 and U-138 cells into Matrigel differed by seven-fold (Figure 4Figure 4

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