Establishment and characterization of primary lung cancer cell lines from Chinese population

Zheng, Chao; Sun, Yinghao; Ye, Xiao Lei; Chen, Hai Quan

doi:10.1038/aps.2010.214

Cited by 36 publications

(34 citation statements)

References 34 publications

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“…Many studies have reported the increased invasiveness of CSCs, implicating the involvement of CSCs in the progression and/or development of metastases (46,47). However, most previous in vitro drug screenings on lung cancer patient-derived cancer cells were performed in serum-containing medium (48), whereas tumor spheres in serum-free condition enrich CSC-like populations (49). Herein, PDXs derived from NSCLC brain metastases gave rise to numerous tumor spheres in a few days after mechanical dissociation ex vivo in a reproducible manner, whereas PDXs from NSCLC primary tumor demonstrated poor viability and sphereforming ability in vitro.…”

Section: Discussionmentioning

confidence: 99%

Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy

Lee

et al. 2015

Clinical Cancer Research

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Purpose: The increasing prevalence of distant metastases from non-small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies.Experimental Design: We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment.Results: NSCLC brain metastases (n ¼ 34) showed a significantly higher successful PDX establishment rate than primary specimens (n ¼ 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions.Conclusions: Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments.

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Section: Discussionmentioning

confidence: 99%

Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy

Lee

et al. 2015

Clinical Cancer Research

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“…Briefly, the human clinical samples were rinsed with 1× PBS for 3-5 times and then divided into several pieces with one for dSTORM imaging and one fixed in 4% PFA for immunohistochemistry and H&E analyses. For imaging, the lung cancer specimens were fully minced and homogenized in 1 ml ACL4 medium with 5% FBS [47]; the normal lung tissues were incubated with Collagenase III (Invitrogen, final concentration of 1 mg/ml) at 37 °C for 1-h shaking. These tissues in solution were then passed through a 60-80 µm 2 filter, and the cell suspension was centrifuged at 1 500 rpm for 4 min and resuspended in 1× PBS with 3% bovine serum albumin (BSA) for labeling with FITC anti-human CD326 (EpCAM; Biolegend; diluted at 1:40 ratio by PBS) by shaking at 4 °C in dark for 20 min.…”

Section: Human Specimen Primary Cell Isolation and Pretreatmentmentioning

confidence: 99%

Regulation of EGFR nanocluster formation by ionic protein-lipid interaction

et al. 2014

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The abnormal activation of epidermal growth factor receptor (EGFR) is strongly associated with a variety of human cancers but the underlying molecular mechanism is not fully understood. By using direct stochastic optical reconstruction microscopy (dSTORM), we find that EGFR proteins form nanoclusters in the cell membrane of both normal lung epithelial cells and lung cancer cells, but the number and size of clusters significantly increase in lung cancer cells. The formation of EGFR clusters is mediated by the ionic interaction between the anionic lipid phosphatidylinositol-4,5-bisphosphate (PIP2) in the plasma membrane and the juxtamembrane (JM) region of EGFR. Disruption of EGFR clustering by PIP2 depletion or JM region mutation impairs EGFR activation and downstream signaling. Furthermore, JM region mutation in constitutively active EGFR mutant attenuates its capability of cell transformation. Collectively, our findings highlight the key roles of anionic phospholipids in EGFR signaling and function, and reveal a novel mechanism to explain the aberrant activation of EGFR in cancers.

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“…, Lkb1 L/L mice and prepared for primary cell culture as described previously 10 as well as for histopathology examination and genotyping identification.…”

Section: G12dmentioning

confidence: 99%

NEDD9 promotes lung cancer metastasis through epithelial-mesenchymal transition

Jin

Zheng

et al. 2013

Int. J. Cancer

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Metastasis is the major cause for high mortality of lung cancer with the underlying mechanisms poorly understood. The scaffolding protein neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) has been identified as a prometastasis gene in several types of cancers including melanoma and breast cancer. However, the exact role and related mechanism of NEDD9 in regulating lung cancer metastasis still remain largely unknown. Here, we demonstrate that NEDD9 knockdown significantly inhibits migration, invasion and metastasis of lung cancer cells in vitro and in vivo. The pro-metastasis role of Nedd9 in lung cancer is further supported by studies in mice models of spontaneous cancer metastasis. Moreover, we find that NEDD9 promotes lung cancer cell migration and invasion through the induction of epithelial-mesenchymal transition (EMT) potentially via focal adhesion kinase activation. More importantly, NEDD9 expression inversely correlates with Ecadherin expression in human lung cancer specimens, consistent with the findings from in vitro studies. Taken together, this study highlights that NEDD9 is an important mediator promotes lung cancer metastasis via EMT.Lung cancer is a deadly disease with high mortality and its 5-year survival rate is approximately 15% globally. Metastasis, frequently observed in patients initially diagnosed with lung cancer, remains as an important factor in contribution to high mortality of lung cancer.1 Despite great efforts in last decades, the molecular mechanisms involved in lung cancer metastasis process still remain far from being fully understood.Recent studies have shown that NEDD9 (Neural precursor cell expressed, developmentally down-regulated 9, also known as HEF1), a scaffolding protein without known catalytic activity, is important for pro-metastasis behavior in several types of solid tumors. 2,3 In melanoma, NEDD9 is frequently up-regulated by gene allele amplification and activates FAK (focal adhesion kinase) to promote cell invasion and metastasis.2 NEDD9 complexes with DOCK3 and regulates the activation of Rac which are essential for promoting the mesenchymal-type movement of melanoma cells. 4 In glioblastoma, NEDD9 works as an effector of FAK to promote tumor cell aggression.5 Interestingly, Nedd9 2/2 mice displayed much less mammary tumor formation as well as lung metastasis, which is potentially due to the reduction of Fak and Src activation.6 Consistently, we have recently found that NEDD9 is transcriptionally regulated by CRTC1/CREB complex in LKB1-deficient lung cancer and significantly contributes to tumor progression via the promotion of tumor differentiation status.7 However, the roles of NEDD9 in lung

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Establishment and characterization of primary lung cancer cell lines from Chinese population

Cited by 36 publications

References 34 publications

Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy

Patient-Derived Xenografts from Non–Small Cell Lung Cancer Brain Metastases Are Valuable Translational Platforms for the Development of Personalized Targeted Therapy

Regulation of EGFR nanocluster formation by ionic protein-lipid interaction

NEDD9 promotes lung cancer metastasis through epithelial-mesenchymal transition

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