scholarly journals Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2937
Author(s):  
Lorenza Mautone ◽  
Carlo Ferravante ◽  
Anna Tortora ◽  
Roberta Tarallo ◽  
Giorgio Giurato ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Advanced Disease ◽  
Thyroid Tissue ◽  
Disease Stage ◽  
Driver Gene ◽  
Integrin Expression ◽  
Papillary Thyroid ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion

Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in papillary thyroid carcinomas (PTC). ITGA2, 3, 6, V, and ITGB1 integrin subunits were overexpressed in PTC compared to normal thyroid tissue. The PTC histology variants “classical” and “tall cell” displayed a similar integrin expression profile with a higher level of ITGA3, ITGAV, and ITGB1, which differed from that of the “follicular” variant. Interestingly, compared to RAS mutations, BRAFV600E mutation was associated with a significantly higher expression of integrins. Some integrin subunits were associated with advanced disease stage, lymph node metastasis, extrathyroidal extension, and high-risk groups. Among them, ITGA3 expression displayed the highest correlation with advanced disease and was associated with a negative prognosis. In vitro scratch assay and Matrigel invasion assay in two different PTC cell lines confirmed α3β1 role in cell motility and invasion, supporting its involvement during tumor progression. These results demonstrate the existence of a PTC-specific integrin expression signature correlated to histopathology, specific driver gene mutations, and aggressiveness of the disease.

scholarly journals Effect of nicotine- and tar-removed cigarette smoke extract on cancer metastasis

2021 ◽  
Vol 3 (2) ◽  
pp. 49
Author(s):  
Yuta Takahashi ◽  
Takuya Araki ◽  
Ayumu Nagamine ◽  
Hideaki Yashima ◽  
Daisuke Nagano ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Tumor Metastasis ◽  
Cancer Metastasis ◽  
In Vitro Study ◽  
Cigarette Smoke Extract ◽  
Spontaneous Metastasis ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Cell Invasiveness

Cigarette smoking is known to impact the promotion of carcinogenesis and tumor metastasis. On the other hand, some components in smoke were found to have health-promoting effects, and cancer suppressor effects of components in tobacco smoke have attracted attention. Although some studies showed the cancer suppressive effect of cigarette smoke extract (CSE) in vitro study, the effect of CSE administration on cancer is controversial. In this study, we investigated the effect of CSE-administration on tumor metastasis in a spontaneous tumor metastasis model using B16-BL6 cells, which is more clinical conditions. C57BL/6NCr mice were subcutaneously inoculated B16-BL6 cells into the footpad of the right rear leg. CSE was intraperitoneally administrated for 28 days from the day of inoculation. At 2 weeks after inoculation, the primary focus was excised. Subsequently, survival days of the mice were recorded to determine the effect of CSE-administration on spontaneous metastasis. The effect of CSE, α, β-unsaturated ketones, and aldehydes on B16-BL6 cell invasiveness were confirmed by matrigel invasion assay. Survival days of mice injected with 100% CSE was significantly shortened than that of control. B16-BL6 cell invasiveness was accelerated by the treatment with 0.1% CSE and 3 μM of crotonaldehyde. Intraperitoneal CSE-administration may progress spontaneous metastasis of B16-BL6 cells via enhancement of B16-BL6 cell invasiveness. As the cause, we found that crotonaldehyde contained in CSE may enhance the invasion ability of cancer cells. To clarify the cancer-suppressing effect of tobacco components, the effect of crotonaldehyde-removed CSE on tumor should be assessed in detail. Keywords: cigarette smoke extract (CSE), metastasis, crotonaldehyde (CA), B16-BL6 mouse melanoma cells, invasion 

scholarly journals MPPa-PDT suppresses breast tumor migration/invasion through inhibiting AKT-NF-κB-dependent MMP-9 expressions via ROS

2019 ◽  
Author(s):  
Liyi Huang ◽  
Haidan Lin ◽  
Qing Chen ◽  
Lehua Yu ◽  
Dingqun Bai
Keyword(s):  
Breast Cancer ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Therapeutic Treatment ◽  
Oxygen Scavenger ◽  
Akt Inhibitor ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Mcf 7

Abstract Background: breast cancer is the most commonly women cancer and most breast cancer deaths are related to tumor metastasis. Therefore, inhibiting metastasis may provide a therapeutic treatment for breast cancer. In the present study, pyropheophorbide-α methyl ester mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in breast cancer cells MCF-7. Methods: Uptake of MPPa was detected by fluorescence microscope. Cell viability was evaluated by CCK-8. Generation of ROS were detected by DCFH-DA. Migration of cells was assessed by wound healing assay and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, Phospho-Akt, Phospho-NF-kB p65 and NF-kB p65 were measured by western blotting. F-actin cytoskeleton was observed by immunofluorescence. Lung organs were stained with Hematoxylin and Eosin. Results: Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT down-regulated expression of MMP2 and MMP9 which is responsible for metastasis. MPPa-PDT reduced the phosphorylation of AKT and NF-κB. MPPa-PDT also destroyed cytoskeleton F-actin in MCF-7 cells. These effects were blocked by the reactive oxygen scavenger NAC or AKT activator SC79 while PI3K inhibitor LY294002 or AKT inhibitor Triciribine increased these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion: taken together, these results demonstrated that MPPa-PDT inhibits metastasis of MCF-7 cells both in vitro and vivo, and that may involve in AKT-NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising therapeutic treatment to inhibit metastasis.

scholarly journals Alcohol Promotes Hepatocellular Carcinoma Metastasis Through SIRT7-Dependent EMT Regulation

2021 ◽  
Author(s):  
Chen Zhang ◽  
Jinqiu Zhao ◽  
Jie Zhao ◽  
Bohao Liu ◽  
Wenbin Tang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Critical Factor ◽  
Bioinformatic Analysis ◽  
Disease Stage ◽  
Qrt Pcr ◽  
E Cadherin

Abstract Background Long-term alcohol use is a confirmed risk factor of liver cancer tumorigenesis and metastasis. Multiple mechanisms responsible for alcohol related tumorigenesis have been proposed, including toxic reactive metabolite production, oxidative stress and fat accumulation which trigger hepatocyte cell death and inflammation. However, mechanisms underlying alcohol-mediated liver cancer metastasis remain largely unknown. Methods SIRT7 expression pattern and its association with HCC metastasis were investigated by bioinformatic analysis and verified by western blot and immunochemistry in HCC tissues. The biological consequences of overexpression and knockdown of SIRT7 in HCC metastasis were studied in vitro and in vivo. qRT-PCR, immunofluorescence assay, ChIP assay were utilized to assess the effects of SIRT7 on E-cadherin expression. Effects of alcohol on SIRT7 expression were evaluated by qRT-PCR, immunofluorescence and inhibitor treatments and pulmonary metastasis model mice fed with Lieber Decarli alcohol diet were used to clarify the mechanisms by which SIRT7 facilitated alcohol mediated HCC metastasis. Results SIRT7 is a critical factor in promoting liver cancer metastasis. SIRT7 expression is closely associated with disease stage and high SIRT7 predicts worse overall and disease-free survival. Overexpression of SIRT7 promotes HCC cell migration and EMT while knockdown of SIRT7 showed opposite effects. Mechanistically, we found that SIRT7 suppresses E-Cadherin expression through promoter binding and H3K18 deacetylation. Most importantly, we identified that alcohol upregulates SIRT7 expression in hepatocyte both in vitro and in vivo. Reducing SIRT7 activity completely abolished alcohol-mediated liver cancer metastasis in vivo. Conclusion SIRT7-dependent EMT regulation is a pivotal regulatory mechanism of alcohol-mediated HCC metastasis and reveals previously unidentified roles of SIRT7 in promoting EMT and metastasis in human HCC. Therapeutic strategies that inhibit SIRT7 may offer novel options for the treatment of HCC.

Blocking pro-invasive signaling and inflammatory activation in triple-negative breast cancer with nucleic-acid scavengers (NASs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13096-e13096
Author(s):  
Elias Eteshola ◽  
Karenia Landa ◽  
Eun-Sil Shelley Hwang ◽  
Smita Nair ◽  
Bruce Sullenger
Keyword(s):  
Breast Cancer ◽  
Nucleic Acid ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Chemotherapeutic Agents ◽  
Metastatic Progression ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Insight Into

e13096 Background: Breast cancers remain the most lethal malignancies amongst women worldwide and the second leading cause of cancer-related mortalities in the US. Subtype heterogeneity and aggressive invasive potential are believed to be the major contributors of these outcomes. Triple-negative breast cancer (TNBC) are notoriously aggressive, difficult-to-treat, and metastatic. Inflammation-driven tumorigenesis has been shown to correlate with cell-free DNA (cfDNA) and other damage-associated molecular patterns (DAMPs) in cancer patient sera. We showed that nucleic-acid scavengers (NAS) can block pro-inflammatory signals elicited by DAMP-activation of innate immune sensors (e.g. toll-like receptors). Treatment with the NAS PAMAM-G3 drastically reduced liver metastatic burden in an immunocompetent murine model of pancreatic cancer. Methods: TNBC cells lines were treated with a cocktail of standard-of-care chemotherapeutic agents and the conditioned media (CM) from these cells served as an in vitro DAMP source. Downstream function of TLR activation was tested via a HEK293-TLR reporter cell line measuring absorbance at 655nm. The in vitro invasive phenotype was tested and quantified using a Transwell-Matrigel invasion assay. Cytokine secretion was measured using a BioLegend cytokine array. Results: TNBC CM greatly increased TNBC cell invasion in vitro and that treatment with the NAS PAMAM-G3 significantly inhibits this effect. Treatment of human monocytes (THP-1) with TNBC CM elicited a strong pro-inflammatory response with elevated levels of IL-8, IL-6, CCL2, and IL-1β. Other biologically immune responders including human PBMCs will be tested to determine the potential impact on the tumor immune microenvironment during tumorigenesis and treatment. Conclusions: To elucidate the mechanism by which this NAS works in these tumor settings, our lab has developed several PAMAM-G3 derivatives, including biotin, IR-, and near-IR fluorophore labeled molecules. These molecules will allow us to capture and characterize DAMPs and do in vivo live imaging experiments to gain insight into NAS PK/PD properties. This insight into NAS capabilities will enhance our understanding of metastatic progression and its interplay with the immune system. Moreover, these principles will aid in the development of novel of anti-metastatic therapies to improve TNBC patient outcomes.

The role of human tissue kallikreins 7 and 8 in intracranial malignancies

2006 ◽  
Vol 387 (12) ◽  
pp. 1607-1612 ◽  
Author(s):  
Panagiotis Prezas ◽  
Andreas Scorilas ◽  
Christina Yfanti ◽  
Petar Viktorov ◽  
Niki Agnanti ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Matrigel Invasion Assay ◽  
Altered Expression ◽  
Matrigel Invasion ◽  
Cox Proportional Hazard ◽  
Brain Tumor Cells ◽  
Invasive Capacity ◽  
The Central Nervous System ◽  
Cox Proportional Hazard Regression

Abstract Recent evidence suggests that many tissue kallikreins are implicated in carcinogenesis. Kallikrein 8 (KLK8) plays a role in the physiology of the central nervous system. Kallikrein 7 (KLK7) takes part in skin desquamation. Both show altered expression in ovarian and breast cancer. In this study, we examined the level of mRNA expression of the KLK7 and KLK8 genes in 73 intracranial tumors using qualitative RT-PCR. The results were correlated with clinical and histomorphological variables and patient outcome. The expression of both genes was also examined in the brain cancer cell lines U-251 MG, D54 and SH-SY5Y and the invasive capacity of glioblastoma cells U-251 MG overexpressing hK7 or hK8 was also investigated in an in vitro Matrigel assay. Follow-up analysis revealed that expression of KLK7 mRNA was associated with shorter overall survival (OS) compared to patients with no KLK7 expression, as determined by Cox proportional hazard regression analysis. Overexpression of hK7 protein by cultivated brain tumor cells significantly enhanced the invasive potential in the Matrigel invasion assay, in contrast to cells overexpressing hK8 protein. Our data suggest that hK7 protein overexpression is associated with a more aggressive phenotype in brain cancer cells.

scholarly journals Lentivirus-Mediated Nox4 shRNA Invasion and Angiogenesis and Enhances Radiosensitivity in Human Glioblastoma

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yongsheng Li ◽  
Na Han ◽  
Tiejun Yin ◽  
Lulu Huang ◽  
Shunfang Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Survival Curve ◽  
Cell Counting ◽  
Ros Production ◽  
Glioblastoma Cells ◽  
Cellular Functions ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Migration Potential

Radioresistance remains a significant therapeutic obstacle in glioblastoma. Reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation and apoptosis. Nox4 NADPH oxidase is abundantly expressed and has proven to be a major source of ROS production in glioblastoma. Here we investigated the effects of Nox4 on GBM tumor cell invasion, angiogenesis, and radiosensitivity. A lentiviral shRNA vector was utilized to stably knockdown Nox4 in U87MG and U251 glioblastoma cells. ROS production was measured by flow cytometry using the fluorescent probe DCFH-DA. Radiosensitivity was evaluated by clonogenic assay and survival curve was generated. Cell proliferation activity was assessed by a cell counting proliferation assay and invasion/migration potential by Matrigel invasion assay. Tube-like structure formation assay was used to evaluate angiogenesis abilityin vitroand VEGF expression was assessed by MTT assay. Nox4 knockdown reduced ROS production significantly and suppressed glioblastoma cells proliferation and invasion and tumor associated angiogenesis and increased their radiosensitivityin vitro. Our results indicate that Nox4 may play a crucial role in tumor invasion, angiogenesis, and radioresistance in glioblastoma. Inhibition of Nox4 by lentivirus-mediated shRNA could be a strategy to overcome radioresistance and then improve its therapeutic efficacy for glioblastoma.

scholarly journals PDK1 Activity Regulates Proliferation, Invasion and Growth of Hemangiomas

2015 ◽  
Vol 36 (5) ◽  
pp. 1903-1910 ◽  
Author(s):  
Ningning Zheng ◽  
Xudong Ding ◽  
Amy Sun ◽  
Rabita Jahan
Keyword(s):  
Signaling Pathway ◽  
Vascular Endothelial Cell ◽  
Vascular Tumor ◽  
Akt Signaling ◽  
Vascular Tumors ◽  
Akt Signaling Pathway ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Proliferation And Invasion

Background: Hemangiomas are common vascular endothelial cell tumors. Abnormally activated PI3K/Akt signaling pathway is one of the most important biological characteristics of Hemangioma. 3-phosphoinositide-dependent kinase 1(PDK1), an upstream protein of Akt, regulates the activity of Akt and its downstream kinases. The objective of this study is to explore the effect of PDK1 on malignant vascular tumors and their cell signaling mechanism in mice. Methods: Mouse Hemangioendothelioma Endothelial Cells (EOMA cells) and Nu/Nu mice were used. The silencing of PDK1 was mediated by lentiviral shRNA. Western blotting, WST-1 proliferation assay, Matrigel invasion assay, and Xenograft vascular tumor model were utilized to examine the effects and mechanism of PDK1 growth, proliferation, and invasion of an Hemangioma. Results: PDK1 deficiency significantly reduced the proliferation and invasion of EOMA cells in vitro, and depressed the growth of vascular tumor in vivo by decreasing the activity of Akt signaling pathway. Conclusion: We hypothesize that PDK1 plays a significant role in the progression and growth of vascular tumors and targeting PDK1 may thus be considered in their treatment.

Investigating an orally available small-molecule inhibitor (vemurafenib) of BRAFV600E in a novel preclinical model of human papillary thyroid cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17014-e17014
Author(s):  
Mark Duquette ◽  
Peter M. Sadow ◽  
Carmen Priolo ◽  
Andrew Fischer ◽  
Richard Hodin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Therapeutic Efficacy ◽  
Thyroid Tissue ◽  
Genetic Alterations ◽  
Preclinical Model ◽  
Papillary Thyroid ◽  
Differentiation Markers ◽  
Therapeutic Model

e17014 Background: Patients with BRAFV600E-positive human papillary thyroid cancer (PTC) have poorer prognosis, higher rates of metastases and mortality, and resistance to radioiodine treatment. The goal of this study was to assess the therapeutic efficacy of vemurafenib (a new orally available BRAFV600E selective inhibitor) in a translational therapeutic model of BRAFV600E human nonmetastatic or metastatic PTC. Methods: We have established in vitro cultures of human primary PTC cells with or without heterozygous BRAFWT/V600E, primary normal thyroid (NT) cells, and used previously established human PTC cell lines with BRAFV600E. Immunocytochemistry was used to characterize markers of differentiation. Genotyping (over 500 genes analyzed) by mass spectrometry was performed to determine genetic alterations. Cell viability assays were performed upon different concentrations of vemurafenib: 0.01, 0.1, 1, 5, and 10 µM. Phosphorylation (p) of ERK1/2 (downstream BRAFV600E) was used to measure BRAFV600E activity. Results: We have isolated 8 independent batches of primary human non-metastatic or metastatic PTC cells from total thyroidectomy patients with PTC >1.1 cm, and 4 independent batches of primary NT cells from normal matched thyroid tissue specimens. 62.5% of the isolated batches of PTC cells were heterozygous BRAFWT/V600E and expressed epithelial markers and thyroid differentiation markers (e.g. PAX8, TSH-receptor). The NT cells showed no mutations. BRAFWT/V600E nonmetastatic PTC cells showed decreased viability (IC50: 5 µM) and pERK1/2 levels (IC90: 10 µM) when exposed to vemarufenib, with no toxic effects. PTC cells with BRAFWT, or NT cells showed no change in viability and pERK1/2 levels when exposed to vemarufenib. Importantly, BRAFWT/V600E metastatic PTC cells showed a partial suppression of viability and inhibition of pERK1/2 but only at a higher dose (10 µM) of vemurafenib. Conclusions: We have established the first translational therapeutic model of heterozygous BRAFWT/V600E-PTC. Testing of PTC samples for BRAFWT/V600E and testing in vitro will help predict therapeutic efficacy of Vemurafenib in patients with BRAFWT/V600E-PTC.

223. Interleukin-11 inhibits human trophoblast invasion via STAT-3 and not MAPK, indicating a likely role in the decidual restraint of trophoblast invasion during placentation

2008 ◽  
Vol 20 (9) ◽  
pp. 23
Author(s):  
P. Paiva ◽  
L. A. Salamonsen ◽  
U. Manuelpillai ◽  
E. Dimitriadis
Keyword(s):  
Western Blot ◽  
Plasminogen Activator ◽  
Mitogen Activated Protein Kinase ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Integrin Expression ◽  
Human Trophoblast ◽  
Matrigel Invasion ◽  
Pai 1

Successful pregnancy depends on the precise regulation of extravillous trophoblast (EVT) invasion into the uterine decidua, primarily by decidua-derived factors. In humans, during early pregnancy, interleukin (IL)-11 is maximally expressed in the decidua1, with its receptor, IL-11-receptor α (Rα) also identified on invasive EVT in vivo2. While a role for IL-11 in EVT migration has been established2, whether it also plays a role in regulating EVT invasion is unknown. We investigated whether IL-11 influences human EVT invasion and the signalling pathways and underlying mechanisms involved using the HTR-8/SVneo immortalised EVT cell-line and primary EVT as models for EVT. The effect of IL-11 on tyrosine phosphorylation (p) of signal transducer and activator of transcription (STAT)-3 was determined by Western Blot. EVT invasion was assessed using in vitro Matrigel invasion assays. To elucidate the mechanisms by which IL-11 may influence EVT invasion, matrix metalloproteinase (MMP) and urokinase plasminogen activator (uPA) activity were assessed by gelatin and plasminogen zymography / uPA activity assay respectively. Tissue inhibitor of MMPs (TIMPs)-1 and –2, plasminogen activator inhibitor (PAI)-1 and –2 and uPA receptor (uPAR) were assessed by ELISA whereas TIMP-3 was assessed by Western Blot. EVT adhesive properties and integrin expression were assessed by in vitro adhesion assays. IL-11 (100 ng/mL) significantly inhibited invasion of EVT cells by 40–60% (P < 0.001). This effect was abolished by inhibitors of STAT-3 but not of mitogen-activated protein kinase pathways. IL-11 (100 ng/mL) had no effect on MMP-2 and –9, TIMP 1–3, uPA, uPAR, PAI-1 and –2 in EVT conditioned media and / or cell lysates. IL-11 (100 ng/mL) also did not regulate EVT cell adhesion or integrin expression. These data demonstrate that IL-11 inhibits human EVT invasion via STAT-3 indicating an important role for IL-11 in the decidual restraint of EVT invasion during normal pregnancy. (1) Dimitriadis et al. (2003) Reprod Biol Endocrinol. 1, 34–38 (2) Paiva et al. (2007) Endocrinol. 148, 5566–72

scholarly journals TMIC-21. TARGETING INVADOPODIA TO BLOCK IONIZING RADIATION-INDUCED GLIOBLASTOMA CELL INVASION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi251-vi252
Author(s):  
Lisa Decotret ◽  
Kevin Bennewith
Keyword(s):  
Ionizing Radiation ◽  
Cell Invasion ◽  
Clonogenic Survival ◽  
Tumour Cells ◽  
High Rate ◽  
Surrounding Tissue ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Human Gbm

Abstract BACKGROUND Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumour that is considered incurable. The majority of GBM patients have a median survival of 15 months despite undergoing extensive treatment. The principal reason for poor outcome is a high rate of recurrence, often due to the tumours cells escaping therapy by infiltrating into the surrounding healthy brain tissue. Previous work from our lab suggests tumour cells that survive radiation therapy (RT) exhibit a more aggressively metastatic phenotype. We hypothesize that RT may increase GBM cell invasion by promoting the activity of invadopodia. Invadopodia are protrusions of the plasma membrane that secrete matrix metalloproteinases to degrade surrounding tissue. Further understanding of the mechanisms by which RT regulates invadopodial biology may lead to new therapeutic strategies to slow or halt the invasion of GBM cells and extend the lives of patients. RESULTS Three human GBM cell lines were exposed to 0, 2, or 5 Gy of ionizing radiation (IR) prior to quantification of cell viability by clonogenic survival assays. Invasion was investigated using a Transwell Matrigel Invasion Assay 48 hours post-IR. Exposure to 2 Gy IR increased invasion of LN229 and U87-MG cells but not LN18 cells. These data suggest that clinically relevant levels of radiation (2 Gy) increases the invasiveness of a subset of GBM cells in vitro. We are currently analyzing proteomic changes in LN229, U87-MG, and LN18 cells post-IR to identify novel drivers of IR-induced GBM cell invasion. Future work will involve genetically or pharmacologically inhibiting the proteins identified via mass spectrometry to determine their role in therapy induced invadopodia-mediated GBM cell invasion. SIGNIFICANCE: Recent evidence suggests tumour cells that survive RT exhibit a more aggressive phenotype. Identifying novel therapeutic targets to limit IR-induced GBM invasion may help to increasing the efficacy of current brain cancer therapy.

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