Interaction between neoplastic cells and cancer-associated fibroblasts through the CXCL12/CXCR4 axis: Role in non–small cell lung cancer tumor proliferation

Slides:

Advertisements

Similar presentations

Stephen R. Broderick, MD, MPHS

Advertisements

Antitumor Efficacy of the Anti-Interleukin-6 (IL-6) Antibody Siltuximab in Mouse Xenograft Models of Lung Cancer Lanxi Song, MS, Matthew A. Smith, PhD,

NDRG1/Cap43/Drg-1 may Predict Tumor Angiogenesis and Poor Outcome in Patients with Lung Cancer Koichi Azuma, MD, PhD, Akihiko Kawahara, PhD, Satoshi.

Michael F. Nentwich, MD, Benjamin A. Bohn, MD, Faik G

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer.

Comparison between adult and infant lung injury in a rabbit ischemia-reperfusion model Wanshan Qiu, MD, Liang Zheng, MD, Haiyong Gu, MD, Duan Chen, MD,

Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR- Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients.

Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps Rahmi Oklu,

Association of CD14+ monocyte-derived progenitor cells with cardiac allograft vasculopathy Mohamed Salama, MD, PhD, Olena Andrukhova, PhD, Susanne Roedler,

Deregulation of SLIT2-Mediated Cdc42 Activity Is Associated with Esophageal Cancer Metastasis and Poor Prognosis Ruo-Chia Tseng, PhD, Jia-Ming Chang,

Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in.

Ugonna N. Ihekweazu, BS, William D. Travis, MD, Raja M. Flores, MD

Bryce J. Laing, MD, David B. Ross, MD, Steven R

Non-small Cell Lung Cancer Induces an Immunosuppressive Phenotype of Dendritic Cells in Tumor Microenvironment by Upregulating B7-H3 Thomas Schneider,

Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats

Characterization of microRNA transcriptome in tumor, adjacent, and normal tissues of lung squamous cell carcinoma Jun Wang, MD, PhD, Zhi Li, MD, PhD,

Interleukin-17 and Prostaglandin E2 Are Involved in Formation of an M2 Macrophage- Dominant Microenvironment in Lung Cancer Lunxu Liu, MD, PhD, Dongxia.

Prognostic Significance of TAZ Expression in Resected Non-Small Cell Lung Cancer Mian Xie, MD, PhD, Li Zhang, MD, Chao-Sheng He, MD, Jin-Hui Hou, MD,

In the Hunt for Therapeutic Targets: Mimicking the Growth, Metastasis, and Stromal Associations of Early-Stage Lung Cancer Using a Novel Orthotopic Animal.

Exogenous surfactant attenuation of ischemia–reperfusion injury in the lung through alteration of inflammatory and apoptotic factors Bart P. van Putte,

Quantitative analysis of survival of transplanted smooth muscle cells with real-time polymerase chain reaction Tamotsu Yasuda, MD, PhD, Richard D. Weisel,

Patrick S. Wolf, MD, Heather E. Merry, MD, Alexander S

Intraoperative detection of lymph node micrometastasis with flow cytometry in non– small cell lung cancer Manabu Ito, MD, Yoshihiro Minamiya, MD, PhD,

Justin D. Blasberg, MD, Chandra M. Goparaju, PhD, Harvey I

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non–heart-beating donors Boming Dong, MD, PhD, Paul.

Pulmonary Fibroblasts Induce Epithelial Mesenchymal Transition and Some Characteristics of Stem Cells in Non-Small Cell Lung Cancer Yasushi Shintani,

IL-17 enhances the migration of B cells during asthma by inducing CXCL13 chemokine production in structural lung cells Roua Al-Kufaidy, MS, Alejandro.

Combining the Multitargeted Tyrosine Kinase Inhibitor Vandetanib with the Antiestrogen Fulvestrant Enhances Its Antitumor Effect in Non-small Cell Lung.

Stem cells and bronchial stump healing

A novel biomarker for the detection of esophageal adenocarcinoma

Clinical and biological significance of stem-like CD133+CXCR4+ cells in esophageal squamous cell carcinoma Chunlai Lu, MD, Fengkai Xu, MD, Jie Gu, MD,

Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in.

Keratinocyte growth factor accelerates compensatory growth in the remaining lung after trilobectomy in rats Keitaro Matsumoto, MD, Takeshi Nagayasu,

Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non– Small Cell Lung Cancer Xenograft Models Josephine Hai, PhD, Shingo Sakashita,

P16Ink4a Suppression of Lung Adenocarcinoma by Bmi-1 in the Presence of p38 Activation Mi-Ok Lee, MSc, Hyeon-Jae Lee, MD, Mi-Ae Kim, MD, Eun-Kyung Kim,

Endothelial progenitor cells attenuate the lung ischemia/reperfusion injury following lung transplantation via the endothelial nitric oxide synthase pathway

Interleukin-22 Is Frequently Expressed in Small- and Large-Cell Lung Cancer and Promotes Growth in Chemotherapy-Resistant Cancer Cells Sebastian Kobold,

MicroRNA-101 Exerts Tumor-Suppressive Functions in Non-small Cell Lung Cancer through Directly Targeting Enhancer of Zeste Homolog 2 Ji-guang Zhang,

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non–Small Cell Lung Cancer Seiichi Ikeda, MSc, Tatsuro Okamoto, MD,

Non-small Cell Lung Cancer Induces an Immunosuppressive Phenotype of Dendritic Cells in Tumor Microenvironment by Upregulating B7-H3 Thomas Schneider,

Interstitial tumor-associated macrophages combined with tumor-derived colony- stimulating factor-1 and interleukin-6, a novel prognostic biomarker in non–small.

Cardiac stem cells in the real world

The lord of the rings Antonio Miceli, MD, PhD

Perioperative cyclooxygenase 2 inhibition to reduce tumor cell adhesion and metastatic potential of circulating tumor cells in non–small cell lung cancer

IL-6 Secreted from Cancer-Associated Fibroblasts Mediates Chemoresistance in NSCLC by Increasing Epithelial-Mesenchymal Transition Signaling Yasushi.

Is tissue the issue? Brian E. Louie, MD, MHA, MPH, FRCSC, FACS

Volume 132, Issue 4, Pages (April 2007)

Yang Zhang, MD, Haiquan Chen, MD, PhD

Volume 135, Issue 2, Pages e2 (August 2008)

Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma Po-Kuei Hsu, MD,

Impact of positive pleural lavage cytology on survival in patients having lung resection for non–small-cell lung cancer: An international individual patient.

Identification and characterization of stemlike cells in human esophageal adenocarcinoma and normal epithelial cell lines Ronghua Zhao, MD, PhD, Luca.

A first start for lung transplantation?

Demonstration of persistent tumor cells 4 weeks after radiofrequency ablation of a pulmonary adenocarcinoma Stéphane Renaud, Marco Schiavon, MD, Nicola.

ALK Translocation in Non-small Cell Lung Cancer with Adenocarcinoma and Squamous Cell Carcinoma Markers Samuel J. Klempner, MD, David W. Cohen, MD, Daniel.

Stephen R. Broderick, MD, MPHS

Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and.

Ly6/uPAR-Related Protein C4

Video-assisted resection for lung cancer results in fewer complications Lunxu Liu, PhD, MD, FRCS The Journal of Thoracic and Cardiovascular Surgery

Nonintubated thoracoscopic surgery for pulmonary lesions in both lungs

The Journal of Thoracic and Cardiovascular Surgery

Discussion The Journal of Thoracic and Cardiovascular Surgery

Linda W. Martin, MD, MPH, FCCP, FACS, Gail E

Robert J. Cerfolio, MD, FACS, FCCP, Ayesha S. Bryant, MSPH, MD

Aritoshi Hattori, MD, Kenji Suzuki, MD

Of mice and men… The Journal of Thoracic and Cardiovascular Surgery

Who should decide margin length in pulmonary excision of lung cancer?

Signal Transducer and Activator of Transcription 3 as Molecular Therapy for Non–Small- Cell Lung Cancer Cheng-Yi Wang, MD, Ting-Ting Chao, PhD, Wei-Tien.

Samuel Kim, MD The Journal of Thoracic and Cardiovascular Surgery

Reappraise the advanced technique for tumor localization and sentinel lymph node assessment in clinical early-stage non–small cell lung cancer Chengwu.

Presentation transcript:

Interaction between neoplastic cells and cancer-associated fibroblasts through the CXCL12/CXCR4 axis: Role in non–small cell lung cancer tumor proliferation Ori Wald, MD, PhD, Uzi Izhar, MD, Gail Amir, MD, Sophie Kirshberg, BSc, Zippora Shlomai, MSc, Gideon Zamir, MD, Amnon Peled, PhD, Oz M. Shapira, MD The Journal of Thoracic and Cardiovascular Surgery Volume 141, Issue 6, Pages 1503-1512 (June 2011) DOI: 10.1016/j.jtcvs.2010.11.056 Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 A, Expressions of CXCL12 and CXCR4 in non–small cell lung cancer tissue samples and plasma polymerase chain reaction assays for CXCL12, CXCR4, and β-actin in 3 non–small cell lung cancer tumors. B, Enzyme-linked immunosorbent assay for CXCL12 concentration in fresh tumor tissue and in the serum of patients operated on for non–small cell lung cancer; 4 cases are shown. C through H, Immunohistochemical staining for CXCL12. C, Tumor-adjacent normal lung tissue. D, CXCL12-positive fibroblasts surrounding CXCL12-negative adenocarcinoma cells. E, CXCL12-positive fibroblasts and vascular structures surrounding CXCL12-negative adenocarcinoma cells. F, Both adenocarcinoma cells and tumor stroma staining positively for CXCL12. G, CXCL12-positive fibroblasts and vascular structures surrounding CXCL12-negative squamous carcinoma cells. H, CXCL12-positive squamous cell carcinoma. I, CXCR4-positive adenocarcinoma. The Journal of Thoracic and Cardiovascular Surgery 2011 141, 1503-1512DOI: (10.1016/j.jtcvs.2010.11.056) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Production of non–small cell lung cancer–derived neoplastic and carcinoma-associated fibroblast cell lines. Hematoxylin and eosin staining of cancer epithelial cells (A) and cancer-derived fibroblasts (B). Cancer epithelial cells stained positively for cytokeratin (C) and negatively for fibronectin (E). Carcinoma-associated fibroblasts were cytokeratin negative (D) and fibronectin positive (F). The Journal of Thoracic and Cardiovascular Surgery 2011 141, 1503-1512DOI: (10.1016/j.jtcvs.2010.11.056) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Characterization of non–small cell lung cancer–derived neoplastic cell lines. A, Polymerase chain reaction results for CXCL12, CXCR4, and β-actin in the cancer epithelial cell lines L3, L4, and A549. B, ELISA assay for CXCL12 secretion to the medium at 24, 48, and 72 hours after plating of L3, L4, and A549 cells. C, Flow cytometric analysis of CXCR4 expressions by L3, L4, and A549. Representative forward and side scatter dot plot and cell gating of L3 is shown at right. Histogram of control antibody and overlay with anti CXCR4 antibody for L3, L4, and A549 are shown at left. Representative hematoxylin and eosin (D and E) and cytokeratin (F) staining of L4-derived tumors forming in the lungs of NOD-SCID mice after injection of the cells into the tail vein. SSC, Side scatter; FSC, forward scatter; PE, phycoerythrin. The Journal of Thoracic and Cardiovascular Surgery 2011 141, 1503-1512DOI: (10.1016/j.jtcvs.2010.11.056) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Characterization of non–small cell lung cancer–derived carcinoma-associated fibroblast cell lines. A, Polymerase chain reaction results for CXCL8, CXCL12, CCL2, and β-actin in 2 carcinoma-associated cell lines, F1 and F2. B, Enzyme-linked immunosorbent assay results for CXCL12 secretion to the medium at 24, 48, and 72 hours after plating of F1 and F2 cells. C, Immunohistochemical staining for CXCR4; black arrows point to CXCR4-positive fibroblast. D, Flow cytometric analysis of CXCR4 expression by carcinoma-associated fibroblast cell lines F1, F2, and F3. Histogram of control antibody and overlay with anti-CXCR4 antibody for F1, F2, and F3 are shown. PE, Phycoerythrin. The Journal of Thoracic and Cardiovascular Surgery 2011 141, 1503-1512DOI: (10.1016/j.jtcvs.2010.11.056) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 CXCL12-induced non–small cell lung cancer proliferation, extracellular signal–regulated kinase phosphorylation, and CCL20 production. A to C, Colony formation by L3, L4, and A549 cells in response to increasing concentration of CXCL12. D to F, Colony formation by L3, L4, and A549 cells in response to increasing concentration of CXCL12 with and without the addition of the CXCR4 antagonist AMD3100. G to I, Western blot analysis for phosphorylated extracellular signal–regulated kinase (Perk, upper panel) and extracellular signal–regulated kinase (erk, lower panel) after stimulation of L3, L4, and A549 cells with CXCL12. J to L, Enzyme-linked immunosorbent assay results for CCL20 secretion after stimulation with increasing concentrations of CXCL12 for L3, L4, and A549 cell lines. M, Enzyme-linked immunosorbent assay results for CCL20 secretion after CXCL12 stimulation with and with out the addition of anti-CXCR4 antibodies or pertussis toxin for L4 cell line. Asterisk indicates P < .05; double asterisk indicates P < .01. The Journal of Thoracic and Cardiovascular Surgery 2011 141, 1503-1512DOI: (10.1016/j.jtcvs.2010.11.056) Copyright © 2011 The American Association for Thoracic Surgery Terms and Conditions