4.6 Article

Bulk tumour cell migration in lung carcinomas might be more common than epithelial-mesenchymal transition and be differently regulated

Journal

BMC CANCER
Volume 18, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s12885-018-4640-y

Keywords

Lung cancer; Bulk migration; Squamous cell carcinoma; Adenocarcinoma; Protein expression; Twist; Mad; Tks5; Cadherin

Categories

Ask authors/readers for more resources

Background: Epithelial-to-mesenchymal transition (EMT) is one mechanism of carcinoma migration, while complex tumour migration or bulk migration is another-best demontrated by tumour cells invading blood vessels. Methods: Thirty cases of non-small cell lung carcinomas were used for identifying genes responsible for bulk cell migration, 232 squamous cell and adenocarcinomas to identify bulk migration rates. Genes expressed differently in the primary tumour and in the invasion front were regarded as relevant in migration and further validated in 528 NSCLC cases represented on tissue microarrays (TMAs) and metastasis TMAs. Results: Markers relevant for bulk cancer cell migration were regulated differently when compared with EMT: Twist expressed in primary tumour, invasion front, and metastasis was not associated with TGF beta 1 and canonical Wnt, as Slug, Snail, and Smads were negative and beta-Catenin expressed membraneously. In the majority of tumours, E-Cadherin was downregulated at the invasive front, but not absent, but, coexpressed with N-Cadherin. Vimentin was coexpressed with cytokeratins at the invasion site in few cases, whereas fascin expression was seen in a majority. Expression of ERK1/2 was downregulated, PLC. was only expressed at the invasive front and in metastasis. Brk and Mad, genes identified in Drosophila border cell migration, might be important for bulk migration and metastasis, together with invadipodia proteins Tks5 and Rab40B, which were only upregulated at the invasive front and in metastasis. CXCR1 was expressed equally in all carcinomas, as opposed to CXCR2 and 4, which were only expressed in few tumours. Conclusion: Bulk cancer cell migration seems predominant in AC and SCC. Twist, vimentin, fascin, Mad, Brk, Tsk5, Rab40B, ERK1/2 and PLC. are associated with bulk cancer cell migration. This type of migration requires an orchestrated activation of proteins to keep the cells bound to each other and to coordinate movement. This hypothesis needs to be proven experimentally.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Critical Care Medicine

Impairment of the NKT-STAT1-CXCL9 Axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Caused by Lung Fibrosis

Katharina Jandl, Leigh M. Marsh, Ayse Ceren Mutgan, Slaven Crnkovic, Francesco Valzano, Diana Zabini, Julia Hoffmann, Vasile Foris, Elisabeth Gschwandtner, Walter Klepetko, Helmut Prosch, Holger Flick, Luka Brcic, Izidor Kern, Akos Heinemann, Horst Olschewski, Gabor Kovacs, Grazyna Kwapiszewska

Summary: This study identified a functional link between natural killer T (NKT) cell activation and vascular fibrosis in patients with pulmonary fibrosis-associated pulmonary hypertension (PF-PH). Activation of NKT cells ameliorated vascular remodeling and right ventricular systolic pressure in a mouse model of PF-PH. Furthermore, activation of the STAT1-CXCL9-CXCR3 axis by NKT cell activation reduced collagen deposition in human pulmonary arterial smooth muscle cells and precision-cut lung slices. These findings suggest a novel therapeutic strategy for targeting vascular fibrosis in interstitial lung diseases.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2022)

Article Medical Laboratory Technology

A Combination of MTAP and p16 Immunohistochemistry Can Substitute for CDKN2A Fluorescence In Situ Hybridization in Diagnosis and Prognosis of Pleural Mesotheliomas

Luka Brcic, Nolwenn Le Stang, Florian Gallob, Daniel Pissaloux, Ruth Sequeiros, Sandrine Paindavoine, Jean Claude Pairon, Marie Karanian, Sanja Dacic, Nicolas Girard, Andrew Churg, Franck Tirode, Francoise Galateau-Salle

Summary: Immunohistochemistry for MTAP and p16 can serve as a surrogate for CDKN2A HD in pleural mesotheliomas. Loss of nuclear p16 (<1% staining) and cytoplasmic MTAP (<=30% staining) indicates poor prognosis in pleural mesothelioma patients.

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE (2023)

Article Medicine, General & Internal

Characteristics and Treatment Outcomes in Advanced-Stage Non-Small Cell Lung Cancer Patients with a KRAS G12C Mutation: A Real-World Study

Oliver Illini, Hannah Fabikan, Maximilian Johannes Hochmair, Christoph Weinlinger, Dagmar Krenbek, Luka Brcic, Ulrike Setinek, Angelika Terbuch, Gudrun Absenger, Selma Konjic, Arschang Valipour

Summary: This study retrospectively assessed the clinicopathological features and standard-of-care treatment responses in patients with KRAS(G12C)-mutated advanced non-small cell lung cancer. The study highlights the poor outcomes in this patient population and emphasizes the need for new treatment options and specific molecular testing.

JOURNAL OF CLINICAL MEDICINE (2022)

Article Oncology

Identification and validation of a ferroptosis-related prognostic risk-scoring model and key genes in small cell lung cancer

Suyang Li, Guihuan Qiu, Jun Wu, Jiaxin Ying, Haiyi Deng, Xiaohong Xie, Xinqing Lin, Zhanhong Xie, Yinyin Qin, Yansheng Wang, Xiaodong Ma, Luka Brcic, Mariano Provencio, Yangchao Chen, Chengzhi Zhou, Ming Liu

Summary: Ferroptosis-related genes can serve as prognostic markers for small cell lung cancer (SCLC) patients and are associated with tumor immune infiltration. The expression of TXNIP is highly correlated with immune infiltration and the efficacy of chemotherapy combined with immunotherapy in SCLC patients.

TRANSLATIONAL LUNG CANCER RESEARCH (2022)

Article Oncology

DNA methylation-based machine learning classification distinguishes pleural mesothelioma from chronic pleuritis, pleural carcinosis, and pleomorphic lung carcinomas

Philipp Jurmeister, Maximilian Leitheiser, Peggy Wolkenstein, Frederick Klauschen, David Capper, Luka Brcic

Summary: The combination of DNA methylation analysis and machine learning can reliably differentiate pleural mesothelioma (PM) from chronic pleuritis and lung cancer, including pleomorphic carcinomas. Additionally, the study identifies new candidate genes for PM carcinogenesis and demonstrates that deconvolution of DNA methylation data can provide insights into the composition of the tumor microenvironment.

LUNG CANCER (2022)

Article Pathology

Expression of phosphorylated ribosomal protein S6 in mesothelioma patients - correlation with clinico-pathological characteristics and outcome: results from the European Thoracic Oncology Platform (ETOP) Mesoscape project

Jan Hendrik Rueschoff, Martina Haberecker, Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini, Joachim G. Aerts, Emanuela Felley-Bosco, Michaela B. Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P. Finn, Enrico Silini, Jan von der Thusen, Nesa Marti, Karerina Vervita, Roswitha Kammler, Solange Peters, Rolf A. Stahel, Paul Baas, Isabelle Opitz

Summary: Pleural mesothelioma (PM) is a aggressive malignancy with poor prognosis. Low phosphorylated S6 (pS6) immunoreactivity is significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. In this study, high pS6 expression is associated with lower likelihood of complete resection and shorter OS and PFS in non-epithelioid PM patients.

MODERN PATHOLOGY (2022)

Letter Oncology

Concurrence of a kinase-dead BRAF and an oncogenic KRAS gain-of-function mutation in juvenile xanthogranuloma

Markus G. Seidel, Luka Brcic, Gerald Hoefler, Caroline Hutter, Milen Minkov, Laura Sophie Steffen, Armin Zebisch, Martin Benesch

PEDIATRIC BLOOD & CANCER (2023)

Editorial Material Radiology, Nuclear Medicine & Medical Imaging

18F-FDG PET/CT in Primary Mesothelioma of the Liver

Birgit Pernthaler, Luka Brcic, Reingard Maria Aigner, Michael Fuchsjaeger, Emina Talakic

Summary: This article presents a rare case of primary malignant mesothelioma in the liver, with the patient being a 48-year-old woman who experienced increasing upper abdominal discomfort and inappetence, accompanied by a weight loss of approximately 10 kg. CT and MRI revealed a highly suspicious mass lesion in the liver. F-18-FDG PET/CT performed for staging showed a pathological F-18-FDG uptake of the known liver tumor. Histology and immunohistochemistry indicated mesothelioma of the liver.

CLINICAL NUCLEAR MEDICINE (2023)

Article Oncology

NR4A3 fusions characterize a distinctive peritoneal mesothelial neoplasm of uncertain biological potential with pure adenomatoid/microcystic morphology

Abbas Agaimy, Luka Brcic, Laurence M. Briski, Yin P. Hung, Michael Michal, Michal Michal, G. Petur Nielsen, Robert Stoehr, Andrew E. Rosenberg

Summary: A focal adenomatoid-microcystic pattern is not uncommon in peritoneal mesothelioma, but tumors composed almost exclusively of this pattern are distinctly rare and have not been well characterized. Herein, we describe five peritoneal mesothelial neoplasms that are pure adenomatoid/microcystic in morphology and unified by the presence of an NR4A3 fusion. These tumors showed morphological similarities and lacked a conventional epithelioid or sarcomatoid component. At the last follow-up, all five patients were alive and disease-free.

GENES CHROMOSOMES & CANCER (2023)

Article Cell Biology

Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements

Stephan Ihrler, David Stiefel, Philipp Jurmeister, Ann Sandison, Nicola Chaston, Jan Laco, Nina Zidar, Luka Brcic, Robert Stoehr, Abbas Agaimy

Summary: The formal pathogenesis of salivary carcinosarcoma (SCS) is clarified in this study, showing that it almost always develops from pleomorphic adenoma (PA) and follows a multistep adenoma-carcinoma-sarcoma sequence. This finding suggests that SCS is a rare and unique variant of carcinoma ex PA with secondary sarcomatous overgrowth.

HISTOPATHOLOGY (2023)

Article Biochemistry & Molecular Biology

The Role of Local Inflammation and Hypoxia in the Formation of Hypertrophic Scars-A New Model in the Duroc Pig

Sebastian P. Nischwitz, Julia Fink, Marlies Schellnegger, Hanna Luze, Vladimir Bubalo, Carolin Tetyczka, Eva Roblegg, Christian Holecek, Martin Zacharias, Lars-Peter Kamolz, Petra Kotzbeck

Summary: Persistent inflammation during wound healing is identified as a precipitating factor in the development of hypertrophic scars. However, lack of standardized models and limited evidence for therapeutic approaches hinder research progress. This study aimed to investigate scar formation mechanisms and develop a method for generating standardized hypertrophic scars through prolonged inflammation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Immunology

Cannabinoid receptor 2 plays a pro-tumorigenic role in non-small cell lung cancer by limiting anti-tumor activity of CD8+ T and NK cells

Arailym Sarsembayeva, Melanie Kienzl, Eva Gruden, Dusica Ristic, Kathrin Maitz, Paulina Valadez-Cosmes, Ana Santiso, Carina Hasenoehrl, Luka Brcic, Joerg Lindenmann, Julia Kargl, Rudolf Schicho

Summary: Cannabinoid (CB) receptors, particularly CB2, play an important role in the tumor microenvironment of non-small cell lung cancer (NSCLC). Deficiency of CB2 reduces tumor burden and enhances the activity of immune cells, leading to improved response to anti-PD-1 therapy. CB2 could be a potential adjuvant target for immunotherapy.

FRONTIERS IN IMMUNOLOGY (2023)

Article Biochemistry & Molecular Biology

Cancer-Associated Fibroblasts Influence Survival in Pleural Mesothelioma: Digital Gene Expression Analysis and Supervised Machine Learning Model

Sabrina Borchert, Alexander Mathilakathu, Alina Nath, Michael Wessolly, Elena Mairinger, Daniel Kreidt, Julia Steinborn, Robert F. H. Walter, Daniel C. Christoph, Jens Kollmeier, Jeremias Wohlschlaeger, Thomas Mairinger, Luka Brcic, Fabian D. Mairinger

Summary: The expression level of Fibroblast activation protein alpha (FAP) is associated with the formation of desmoplastic stromal reaction (DSR) in pleural mesothelioma (PM). DSR-high samples demonstrated a significant prolongation of median survival time, indicating the important role of cancer-associated fibroblasts (CAFs) in tumor prognosis. These findings provide a basis for introducing new therapeutic strategies and predictive biomarkers for survival in PM.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Multidisciplinary Sciences

Introducing a new type of alternative laryngeal mucosa model

Tanja Grossmann, Andrijana Kirsch, Magdalena Grill, Barbara Steffan, Michael Karbiener, Luka Brcic, Barbara Darnhofer, Ruth Birner-Gruenberger, Markus Gugatschka

Summary: Research on human vocal fold biology is limited due to the sensitive microstructure of the vocal fold mucosa. We developed an alternative model using human buccal epithelial cells and vocal fold fibroblasts, which closely resembles native vocal fold mucosa in terms of histology and proteomics. This model provides a reproducible in vitro platform for various research opportunities.

PLOS ONE (2023)

Article Respiratory System

Abnormal pulmonary hemodynamics during exercise is associated with exercise capacity in COPD

Teresa Sassmann, Philipp Douschan, Vasile Foris, Natascha Troester, Katarina Zeder, Luka Brcic, Adrienn Tornyos, Gerhard Bachmaier, Michael Fuchsjaeger, Horst Olschewski, Gabor Kovacs

Summary: Even in the absence of significant pulmonary hypertension at rest, COPD patients show characteristic abnormalities in pulmonary hemodynamics during exercise, which may impact exercise capacity.

RESPIRATORY RESEARCH (2022)

No Data Available