The Impact of Non-Lethal Single-Dose Radiation on Tumor Invasion and Cytoskeletal Properties

Hohmann, Tim; Grabiec, Urszula; Vogel, Carolin; Ghadban, Chalid; Ensminger, Stephan; Bache, Matthias; Vordermark, Dirk; Dehghani, Faramarz

doi:10.3390/ijms18092001

Cited by 12 publications

(17 citation statements)

References 86 publications

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“…Thereby, the structure density can be obtained as the structuredness normalized to the cell area. The images were analyzed using a self-written MatLab (The MathWorks, Natick, USA) script, as published before [29].…”

Section: Image Analysis Of Actin Structuresmentioning

confidence: 99%

MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma

et al. 2020

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Background: Metastasis-associated in colon cancer 1 (MACC1) is an established marker for metastasis and tumor cell migration in a multitude of tumor entities, including glioblastoma (GBM). Nevertheless, the mechanism underlying the increased migratory capacity in GBM is not comprehensively explored. Methods: We performed live cell and atomic force microscopy measurements to assess cell migration and mechanical properties of MACC1 overexpressing GBM cells. We quantified MACC1 dependent dynamics of 3D aggregate formation. For mechanistic studies we measured the expression of key adhesion molecules using qRT-PCR, and MACC1 dependent changes in short term adhesion to fibronectin and laminin. We then determined changes in sub-cellular distribution of integrins and actin in dependence of MACC1, but also in microtubule and intermediate filament organization. Results: MACC1 increased the migratory speed and elastic modulus of GBM cells, but decreased cell-cell adhesion and inhibited the formation of 3D aggregates. These effects were not associated with altered mRNA expression of several key adhesion molecules or altered short-term affinity to laminin and fibronectin. MACC1 did neither change the organization of the microtubule nor intermediate filament cytoskeleton, but resulted in increased amounts of protrusive actin on laminin. Conclusion: MACC1 overexpression increases elastic modulus and migration and reduces adhesion of GBM cells thereby impeding 3D aggregate formation. The underlying molecular mechanism is independent on the organization of microtubules, intermediate filaments and several key adhesion molecules, but depends on adhesion to laminin. Thus, targeting reorganization of the cytoskeleton and cell motility via MACC1 may offer a treatment option to impede GBM spreading.

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Section: Image Analysis Of Actin Structuresmentioning

confidence: 99%

MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma

et al. 2020

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“…Interestingly a recent report showed that non-lethal single dose radiation (2 Gy) influenced the invasiveness, cell stiffness and actin cytoskeleton properties of two GBM cell lines, namely, LN229 and U87 [24]. Although the authors reported reduced invasiveness following the 2 Gy irradiation, they found "generalized stiffness" to be a profound marker of the invasiveness of a tumor cell population [24]. This finding by itself is not new.…”

Section: Alteration Of Cell Migration Cancer Metastasis and Physics mentioning

confidence: 98%

“…Moreover, the alteration of migration of both cancer cells and non-cancer cells by radiotherapy, which we have demonstrated here, suggests that the cytoskeletal properties of cells are being altered by the X-ray photon interactions. Interestingly a recent report showed that non-lethal single dose radiation (2 Gy) influenced the invasiveness, cell stiffness and actin cytoskeleton properties of two GBM cell lines, namely, LN229 and U87 [24]. Although the authors reported reduced invasiveness following the 2 Gy irradiation, they found "generalized stiffness" to be a profound marker of the invasiveness of a tumor cell population [24].…”

Section: Alteration Of Cell Migration Cancer Metastasis and Physics mentioning

confidence: 98%

“…Several studies have since then been carried out to document the effects of radiotherapy on cancer cell migration and extensive reviews of these have been done [4,5]. Majority of the results showed that ionizing radiation enhanced the migration of cancer cells including GBM [21,[24][25][26]. A few cases [27,28] of purportedly reduced migration were included in the review [5] but it turns out that one of these [28] actually reported radiation-induced enhancement of migration and not reduction.…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy and chemotherapy alter migration of brain cancer cells before cell death

Merrick

Mimlitz

Weeder

et al. 2020

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Although radiotherapy and most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis strategies alongside chemotherapy and radiotherapy. An important step in the metastatic cascade is migration. It is the first step in metastasis via local invasion. Here we address the question whether ionizing radiation and/or chemotherapy might inadvertently promote metastasis and/or invasiveness by enhancing cell migration. We used a standard laboratory irradiator, Faxitron CellRad, to irradiate both non-cancer (HCN2 neurons) and cancer cells (T98G glioblastoma) with 2 Gy, 10 Gy and 20 Gy of X-rays. Paclitaxel (5 μM) was used for chemotherapy. We then measured the attachment and migration of the cells using an electric cell substrate impedance sensing device. Both the irradiated HCN2 cells and T98G cells showed significantly (p < 0.01) enhanced migration compared to non-irradiated cells, within the first 20 to 40 hours following irradiation with 20 Gy. Our results suggest that cell migration should be a therapeutic target in anti-metastasis/anti-invasion strategies for improved radiotherapy and chemotherapy outcomes.

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“…Several mechanisms that promote this counterproductive effect have been identified, including vascular damage, EMT, and cytokine production [25]. The clinical significance of these findings is still largely unknown and new cell biophysical parameters have to be identified in order to assess how RT treatments can promote increased cell migration [26,27] and enhanced growth of distant metastases [25,28] as well as reduction of cell migration [29,30] and inhibition of distant tumor growth, also known as the abscopal effect [31]. Along this path, we proposed here a continuation of our previous work [29] by the introduction of new biophysical parameters that can be used by different researcher interested into basic and clinical translation of mechanobiology investigation.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Biophysical Migration Parameters for Normal Tissue and Metastatic Cancer Cells After Radiotherapy Treatment

et al. 2020

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A large body of literature has demonstrated that the mechanical properties of microenvironment have a key role in regulating cancer cell adhesion, motility, and invasion. In this work, we have introduced two additional parameters, named cell trajectory extension and area traveled by cell, to describe the tendency of normal tissue and metastatic cancer cells to move in a directional way when they interact with physio-pathological substrates, characterized by stiffnesses of 1-13 kPa, before and after treatment with 2 doses of X-rays (2 and 10 Gy). We interpreted these data by evaluating also the impact of substrate stiffness on 2 morphological parameters which indicate not only the state of cell adhesion, but also cell polarization, prerequisite to directional movement, and the formation of protrusions over cell perimeters. We believe that a so wide analysis can give an efficient and easily readable overview of effects of radiation therapy on cell-ECM crosstalk when used as therapeutic agent.

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The Impact of Non-Lethal Single-Dose Radiation on Tumor Invasion and Cytoskeletal Properties

Cited by 12 publications

References 86 publications

MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma

MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma

Radiotherapy and chemotherapy alter migration of brain cancer cells before cell death

Investigation of Biophysical Migration Parameters for Normal Tissue and Metastatic Cancer Cells After Radiotherapy Treatment

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