Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions

Chandrasekar, Nirmala; Jasti, Sushma L.; Sawaya, Raymond; Kyritsis, Anthanassios P.; Konduri, Santhi D.; Ali‐Osman, Francis; Rao, Jasti S.; Mohanam, Sanjeeva

doi:10.1002/1097-0215(20001201)88:5<766::aid-ijc13>3.0.co;2-y

Cited by 40 publications

(31 citation statements)

References 27 publications

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“…An increased expression of these MMPs was also observed after irradiation of another glioma cell line, U87 MG, but not in LN-18 or LN-229 cells, while the activity of both MMPs was increased in all cell lines. 34,35 These results favor the concept that irradiation might promote invasion-related gene expression. Indeed, X-rays also increase the mRNA levels of integrin ␣ v , in line with previous studies on other glioma cell lines.…”

Section: Discussionmentioning

confidence: 81%

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

Parthymou

Kardamakis

Pavlopoulos

et al. 2004

Intl Journal of Cancer

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Malignant gliomas are angiogenesis dependent and present a remarkable degree of resistance to radiotherapy. In the present work, we studied the effect of irradiation of C6 glioma cells on their proliferation and activation in vitro and on glioma cell-induced angiogenesis in vivo and in vitro. Irradiation of C6 glioma cells decreased cell proliferation in a dosedependent manner. Interestingly, metalloproteinase-2 and -9 expression and secretion, as well as integrin ␣ v expression, increased with elevated doses of X rays 48 hr after irradiation and was mostly evident at the higher doses used. When pre-irradiated C6 cells were implanted on nonirradiated chicken embryo chorioallantoic membranes (CAMs), there was a significant dose-dependent increase in tumor induced angiogenesis, compared to angiogenesis induced by nonirradiated cells. Similar results were obtained when C6 cells were irradiated 48 hr after their inocculation onto nonirradiated CAMs. In the same line, conditioned medium from irradiated C6 cells significantly increased endothelial cell proliferation and migration in vitro, in a manner dependent on the dose of X rays. These results explain at least in part the low effectiveness of radiation therapy of malignant gliomas and support the notion that inhibition of angiogenesis in parallel with radiotherapy may represent a new therapeutic approach. © 2004 Wiley-Liss, Inc. Key words: angiogenesis; endothelial cells; glioma cells; metalloproteinase-2; migration; proliferation; X raysMalignant gliomas, the most common type of brain tumors in adults, present a remarkable degree of neovascularisation and invasiveness into surrounding tissues. 1 These features account for their poor prognosis, and although combinations of surgery, radiotherapy and chemotherapy are used, more than 90% of the patients experience local recurrence and their survival is extremely low. These facts stress the need for more effective therapeutic strategies. 2 Rapid cell proliferation and high invasive capacity of glioma cells are crucial for tumor development and progression. Moreover, induction of angiogenesis is an essential prerequisite for tumor growth and spread, and precedes malignant tumor formation. 3 Angiogenesis is a fundamental process by which new blood vessels are formed from pre-existing ones. It is a very important step in reproduction, development and wound healing. Furthermore, angiogenesis is very important in several pathological mechanisms like carcinogenesis, tumor metastasis and inflammation. 4 Radiation is considered to inhibit angiogenesis through damage to the endothelium. 5,6 However, in vivo studies suggest that ionizing radiation induces vascular endothelial growth factor (VEGF) production 7 and enhances both the formation of new blood vessels 8 -11 and the secondary development of tumors. 11-13 We have previously shown in the in vivo system of the chicken embryo chorioallantoic membrane (CAM) that X-rays enhance angiogenesis induced by C6 glioma cells inoculated onto the tissue immediately after irradiation...

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Section: Discussionmentioning

confidence: 81%

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

Parthymou

Kardamakis

Pavlopoulos

et al. 2004

Intl Journal of Cancer

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“…MMP-2, as integral molecule of the invasion process, was activated by irradiation in a b1-and b3-integrin-dependent manner and by stimulating anti-b1-and anti-b3-integrin antibodies. In controversy with the well-known association of the invasive phenotype with MMP overexpression (Rich et al, 1985;Ballin et al, 1988), the radiation-mediated MMP-2 induction (Engebraaten et al, 1992;Nirmala et al, 2000;Wild-Bode et al, 2001) did not lead to increased A-172 and U-138 invasion. Our controversial data suggest, on the one hand, cell line-specific interactions between basal gelatinolytic MMP-2 activity and the degree of invasiveness and, on the other hand, an inverse cell linespecific interaction between radiation-induced MMP-2 activity and radiation-dependent impairment of invasion.…”

Section: Discussionmentioning

confidence: 95%

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

Cordes¹,

Hansmeier²,

Beinke³

et al. 2003

Br J Cancer

100

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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, 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 b1-and b3-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, b1-and b3-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. b1-and b3-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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“…Angiogenesis triggered by tissue ischemia also requires MMP-9 to restore capillary branching (Murawaki et al, 2000). Radiation markedly increased the level of MMP-9 and its mRNA expression in the cocultures of glioblastoma cells and retinal endothelial cells (Nirmala et al, 2000). On the other hand, the inhibition of radiation-enhanced MMP-9 protein expression with As oligonucleotides significantly suppressed radiation-induced invasion (London et al, 2003).…”

Section: Discussionmentioning

confidence: 98%

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway

et al. 2006

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This study is to investigate the molecular mechanism of radiation-enhanced cell invasiveness of hepatocellular carcinoma (HCC) correlating with clinical patients undergoing radiotherapy and subsequently developing metastasis. Three HCC cell lines (HepG2, Hep3B and Huh7) and normal hepatocyte cell line (CL-48) were irradiated with different doses. The effect of radiation on cell invasiveness was determined using the Boyden chamber assay. Radiation-enhanced invasion capability was evident in HCC cells but not in normal hepatocytes. Invasion was observed in gelatin-coated but not fibronectin-coated or type I collagen-coated membranes. Radiation upregulated matrix metalloproteinase-9 (MMP-9) mRNA level, MMP-9 protein level and MMP-9 activity. MMP-9 antisense oligonucleotides inhibited radiation-induced MMP-9 expression and thereby significantly inhibited radiationinduced HCC invasion. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt chemical inhibitors LY294002 and wortmannin suppressed radiation-induced MMP-9 mRNA expression. Transient transfection with dominantnegative Akt plasmid also showed that the PI3K/Aktsignaling pathway was involved in this radiation-induced MMP-9 expression. Moreover, nuclear factor-jB (NFjB) decoy oligodeoxynucleotide suppressed radiation enhanced MMP-9 promoter activity completely. PI3K/ Akt chemical inhibitors inhibited radiation-induced NFjB-driven luciferase promoter activity. Taken together, our results indicated that sublethal dose of radiation could enhance HCC cell invasiveness by MMP-9 expression through the PI3K/Akt/NF-jB signal transduction pathway.

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Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions

Cited by 40 publications

References 27 publications

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro

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

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway

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