Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Ishihara, Seiichiro; Haga, Hisashi; Yasuda, Motoaki; Mizutani, Takeomi; Kawabata, Kazushige; Shirato, Hiroki; Nishioka, Takeshi

doi:10.1016/j.bbrc.2010.04.150

Cited by 23 publications

(39 citation statements)

References 16 publications

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“…However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes, such as high proliferative ability and invasiveness, which correlate with poor prognosis [2–5]. As shown in our previous studies, lung cancer cells that survive irradiation acquire invasive ability that is dependent on cell-matrix adhesion regulated by integrin β1, cellular contractile force modulated by myosin regulatory light chain (MRLC), and molecular signaling mediated by epidermal growth factor receptor and other molecules [6–8]. However, it is not known how cancer cells survive and generate highly malignant tumors after irradiation.…”

Section: Introductionmentioning

confidence: 99%

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

et al. 2015

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Radiotherapy is effective for treating various types of tumors. However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes that correlate with poor prognosis. It is not known how cancer cells survive and generate malignant tumors after irradiation. Here, we show that activating transcription factor 5 (ATF5) promotes radioresistance and malignancy in cancer cells after irradiation. In the G1-S phase of the cell cycle, cancer cells express high levels of ATF5, which promotes cell cycle progression and thereby increases radioresistance. Furthermore, ATF5 increases malignant phenotypes, such as cell growth and invasiveness, in cancer cells in vitro and in vivo. We have identified a new mechanism for the regeneration of highly malignant tumors after irradiation and shown that ATF5 plays a key role in the process.

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Section: Introductionmentioning

confidence: 99%

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

et al. 2015

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“…In the development of novel siRNA therapeutics, few good cell culture-based models exist for examining the differences in delivery to three-dimensional cultures versus two-dimensional cultures. The development of three-dimensional collagen (Ishihara et al 2010), fibronectin (Zhou et al 2008), or synthetic PEG (Raeber et al 2005) hydrogels to study cell morphology and migration has often been used as an intermediate step between cell culture and in vivo models. Current three-dimensional studies involving siRNA treatments either resort to pretreating cells before embedding in the matrix (Ivanov et al 2008), treatment of cells growing on top of a hydrogel (Lei et al 2010), or nucleic acid-containing hydrogel scaffolds implanted into animal models (Andersen et al 2010).…”

Section: Mechanism Of Entrymentioning

confidence: 99%

siRNA Therapeutic Design: Tools and Challenges

Malefyt¹,

Angart²,

Chan³

et al. 2011

Regulatory RNAs

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Current RNA-based therapeutics are principally focused toward activating the RNA interference (RNAi) pathway through exogenous administration of short interfering RNAs (siRNAs) and sometimes short hairpin RNAs (shRNAs). The promise of RNAi-based therapeutics arises from their broad applicability and excellent specificity. This chapter reviews siRNA design strategies for improving intracellular interactions with the RNAi pathway proteins as well as key characteristics required for the design of optimal delivery vehicles to maximize specific silencing in only the cells of interest. The status of previous and ongoing clinical trials will be described as these provide insight for overcoming future challenges for long-term use of RNAi as a therapeutic modality.

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“…The details of the threedimensional (3D) cell culture are described elsewhere. 3 Cells were allowed to proliferate sterically for 12 days. In this experiment, 95 colonies were observed for H1299 and 116 for H1299-IR.…”

Section: Hypoxic-inducible Factor-1α Might Up-regulate Matrix Metallomentioning

confidence: 99%

“…This result is consistent with the report showing 10 Gy-surviving malignant cells had a tendency to take on an irregular shape and had a highly invasive nature. 3 We then performed the MMP1 luciferase assay. The promoter regions included E-box, Ets, and AP1 sites so the promoter activities of pcDNA (as a control) E1AF, Jun/Fos, and HIF-1α could be measured.…”

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Hypoxic-inducible factor-1α might up-regulate matrix metalloproteinase in subclones that survive 10-Gy X-irradiation

Nishioka

Yamazaki

2011

Jpn J Radiol

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To the best of our knowledge, most studies of irradiation effects on cells have focused on early responses, such as RNA expression and protein levels a few hours later or days after irradiation. Of course, it is important to understand how cells respond to irradiation immediately after exposure. However, most cells die if a large dose is given (e.g., 10 Gy, which is now commonly used for lung cancer). To understand the nature of the surviving cells is probably much more relevant to the clinical situation in terms of residual disease or local recurrence.Here we discuss matrix metalloproteinase 1 (MMP1) in relation with hypoxic inducible factor 1α (HIF-1α). The reasons we focused on these molecules were (1) in our previous experiments using lung carcinoma cell lines, MMP1 mRNA was up-regulated in subclones that survived 10 Gy (data not shown); and (2) recently, several studies have shown that HIF-1α up-regulates MMP1 expression. 1,2 In the present experiment, we fi rst established irradiation-surviving H1299 cells (referred to as H1299-IR). Semi-confl uent H1299 cells were irradiated with 10 Gy and were soon seeded onto a 3-cm culture dish. Twelve days later, all the colonies were harvested, and the cells were stored at −80°. The parent cells were derived from the lung adenocarcinoma cell line H1299. To examine the invasiveness of each cell line, a collagen overlay assay was performed. For this, 1 × 10 3 cells were seeded into a collagen-fi lled cultured dish. The details of the threedimensional (3D) cell culture are described elsewhere. 3 Cells were allowed to proliferate sterically for 12 days. In this experiment, 95 colonies were observed for H1299 and 116 for H1299-IR.Colonies were classifi ed into "spheroid" and "nonspheroid" (Fig. 1). Of the 95 H1299 colonies, 25 (26.3 %) took on a nonspheroid shape, whereas 87 (75.0 %) the 116 H1299-IR colonies were nonspheroid-like (chisquared test, P < 0.01). This result is consistent with the report showing 10 Gy-surviving malignant cells had a tendency to take on an irregular shape and had a highly invasive nature. 3 We then performed the MMP1 luciferase assay. The promoter regions included E-box, Ets, and AP1 sites so the promoter activities of pcDNA (as a control) E1AF, Jun/Fos, and HIF-1α could be measured. The construct is shown in Fig. 2a. The luciferase assay for E1AF, Jun/ Fos, and HIF-1α revealed the following fold changes, with the SD, compared to the control, pcDNA, for H1299 cells: E1AF (1.9 ± 0.1), Jun/Fos (5.6 ± 0.2), and HIF-1α (0.8 ± 0.2), respectively. A statistically significant value was observed for Jun/Fos (Student's t-test, P < 0.01). On the other hand, the respective values for H1299-IR were E1AF (2.2 ± 0.1), Jun/Fos (2.7 ± 0.3), and HIF-1α (3.3 ± 0.2). These results are shown in Fig. 2b. Statistically signifi cant values of P ≤ 0.01 were seen for all transcriptional factors for H1299-IR. Paying attention to their initial (i.e., control) status, 4.6-fold higher MMP1 promoter activity was observed for H1299-IR. On cDNA array analysis, MMP1 mRNA was ...

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Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Cited by 23 publications

References 16 publications

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

siRNA Therapeutic Design: Tools and Challenges

Hypoxic-inducible factor-1α might up-regulate matrix metalloproteinase in subclones that survive 10-Gy X-irradiation

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