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Cancers
Special Issues
Metastasis and Tumor Cell Migration of Solid Tumors
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Metastasis and Tumor Cell Migration of Solid Tumors

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 14335

Special Issue Editors

Prof. Dr. Jens Hoeppner

E-Mail Website
Guest Editor
Department of Surgery, University Medical Center of Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
Interests: surgical oncology; HPB surgery; robotic surgery; minimally invasive surgery; clinical trials; multidisciplinary oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Peter Bronsert

E-Mail Website
Co-Guest Editor
Institute of Surgical Pathology, Medical Center—University of Freiburg, Breisacher Strasse 115a, 79106 Freiburg, Germany
Interests: tumors of the pancreas and biliary system; epithelial–mesenchymal transition; tumor–stroma interactions

Special Issue Information

Dear Colleagues,

The developmental process of local and distant metastasis represents the major and defining trait of malignant tumors, whereby tumor cells sustain the capability to migrate from the initial tumor site, seed, and grow at a location other than that of the initial tumor. To date, nearly 90% of all tumor-related deaths are caused by tumor metastasis. Tumor cell migration and invasion are crucial prognostic factors for tumor treatment response and patients’ five-year overall survival. The mechanisms of tumor cell migration and invasion are the focus of this Special Issue. Tumor cell migration and invasion take place at the tumor–host interface and are accompanied by a desmoplastic stroma reaction. So-called "cancer-associated fibroblasts" are involved in the desmoplastic reaction. Cancer-associated fibroblasts are activated stromal cells that not only surround, supply, and protect the tumor but also provide a soil-and-seed platform for tumor metastases. Another important approach to explaining tumor cell metastases is the epithelial–mesenchymal transition. The epithelial–mesenchymal transition is a fundamental model of embryogenesis in which polarized epithelial cells transform into motile epithelial cells with mesenchymal characteristics. This bi-directional embryonic cell differentiation and migration model, which allows for both epithelial to mesenchymal and, conversely, mesenchymal to epithelial cell differentiation, contains fundamental changes in the behavior and morphology of cells that affect cell migration and cell differentiation. As part of the epithelial–mesenchymal transition, tumor cells discard their morphological and molecular epithelial characteristics and adopt a mesenchymal subtype.

This Special Issue will highlight the role of different aspects of the process of epithelial–mesenchymal transition, tumor–host interface interactions, tumor cell migration, and settlement of metastasis in solid tumor disease in order to improve our understanding of these complex interactions in human cancers.

Prof. Dr. Jens Hoeppner
Dr. Peter Bronsert
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metastasis
  • tumor cell migration
  • EMT
  • MET
  • cancer-associated fibroblasts
  • CAF

Published Papers (6 papers)

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Editorial

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1 pages, 146 KiB  
Editorial
Metastasis and Tumor Cell Migration of Solid Tumors
by Jens Hoeppner and Peter Bronsert
Cancers 2021, 13(21), 5576; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215576 - 08 Nov 2021
Cited by 2 | Viewed by 1379
Abstract
The developmental process of local and distant metastases represents the major and defining trait of malignant tumors, whereby tumor cells sustain the capability to migrate from the initial tumor site, seed, and grow at a location other than that of the initial tumor [...] Read more.
The developmental process of local and distant metastases represents the major and defining trait of malignant tumors, whereby tumor cells sustain the capability to migrate from the initial tumor site, seed, and grow at a location other than that of the initial tumor [...] Full article
(This article belongs to the Special Issue Metastasis and Tumor Cell Migration of Solid Tumors)

Research

Jump to: Editorial, Review

19 pages, 4944 KiB  
Article
Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway
by Guowei Gong, Kumar Ganesan, Qingping Xiong and Yuzhong Zheng
Cancers 2023, 15(3), 758; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030758 - 26 Jan 2023
Cited by 6 | Viewed by 1467
Abstract
Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, [...] Read more.
Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The in vitro anti-tumorigenic and anti-migratory properties of ononin were determined by MTT, colony formation, invasion, and migration in MG-63 and U2OS osteosarcoma cell lines. The results were compared with the standard chemotherapeutic drug, doxorubicin (DOX), as a positive control. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation through the EGFR-Erk1/2 signaling pathways. Additionally, ononin significantly inhibited the invasion and migration of human osteosarcoma cells. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin by inhibiting the protein expressions of EGFR-Erk1/2 and MMP2/9. According to the histological study, ononin had no adverse effect on the liver and kidney. Overall, our findings suggested that ononin could be a potentially effective agent against the development and metastasis of osteosarcoma. Full article
(This article belongs to the Special Issue Metastasis and Tumor Cell Migration of Solid Tumors)
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11 pages, 1127 KiB  
Article
Evaluation of the Hamburg-Glasgow Classification in Pancreatic Cancer: Preoperative Staging by Combining Disseminated Tumor Load and Systemic Inflammation
by Thaer S. A. Abdalla, Valeria Almanfalouti, Katharina Effenberger, Faik G. Uzunoglu, Tarik Ghadban, Anna Dupreé, Jakob R. Izbicki, Klaus Pantel and Matthias Reeh
Cancers 2021, 13(23), 5942; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13235942 - 25 Nov 2021
Cited by 2 | Viewed by 1669
Abstract
This study aims to compare the Hamburg Glasgow Classification (HGC) to Union for International Cancer Control (UICC) classification in patients with pancreatic ductal adenocarcinoma (PDAC). As adequate tumor classification is only possible after tumor resection and histological evaluation, only 20% of patients with [...] Read more.
This study aims to compare the Hamburg Glasgow Classification (HGC) to Union for International Cancer Control (UICC) classification in patients with pancreatic ductal adenocarcinoma (PDAC). As adequate tumor classification is only possible after tumor resection and histological evaluation, only 20% of patients with PDAC receive accurate tumor staging. Thus, an accurate preoperative staging system is still missing but urgently needed. Systemic inflammation and tumor dissemination are important factors regarding the oncological outcome. HGC integrates both into a preoperative staging system, by combining C-reactive protein (CRP), albumin, and disseminated tumor cells (DTC) in the bone marrow. In this prospective study, 109 patients underwent surgical exploration for suspected PDAC. All patients underwent a preoperative bone marrow aspiration for DTC detection. HGC showed significant preoperative risk stratification for overall survival (OS) (p-value < 0.001) and progression-free survival (PFS) (p-value < 0.001). These results were comparable to the UICC survival stratification for OS and PFS (p-value = 0.001 and 0.006). Additionally, in non-metastatic PDAC, HGC III-IV was associated with shorter OS and PFS (p-value < 0.001, respectively) when compared to HGC I-II. Therefore, the HGC is a promising preoperative prognostic staging classification for accurate and simple outcome stratification in patients with PDAC. Full article
(This article belongs to the Special Issue Metastasis and Tumor Cell Migration of Solid Tumors)
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Review

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26 pages, 960 KiB  
Review
Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment
by Asmaa Elrakaybi, Dietrich A. Ruess, Michael Lübbert, Michael Quante and Heiko Becker
Cancers 2022, 14(23), 5926; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235926 - 30 Nov 2022
Cited by 4 | Viewed by 2208
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC. Full article
(This article belongs to the Special Issue Metastasis and Tumor Cell Migration of Solid Tumors)
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13 pages, 1373 KiB  
Review
Role of Epithelial-to-Mesenchymal Transition for the Generation of Circulating Tumors Cells and Cancer Cell Dissemination
by Gaetan Aime Noubissi Nzeteu, Claudia Geismann, Alexander Arlt, Frederik J. H. Hoogwater, Maarten W. Nijkamp, N. Helge Meyer and Maximilian Bockhorn
Cancers 2022, 14(22), 5483; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225483 - 08 Nov 2022
Cited by 7 | Viewed by 2161
Abstract
Tumor-related death is primarily caused by metastasis; consequently, understanding, preventing, and treating metastasis is essential to improving clinical outcomes. Metastasis is mainly governed by the dissemination of tumor cells in the systemic circulation: so-called circulating tumor cells (CTCs). CTCs typically arise from epithelial [...] Read more.
Tumor-related death is primarily caused by metastasis; consequently, understanding, preventing, and treating metastasis is essential to improving clinical outcomes. Metastasis is mainly governed by the dissemination of tumor cells in the systemic circulation: so-called circulating tumor cells (CTCs). CTCs typically arise from epithelial tumor cells that undergo epithelial-to-mesenchymal transition (EMT), resulting in the loss of cell–cell adhesions and polarity, and the reorganization of the cytoskeleton. Various oncogenic factors can induce EMT, among them the transforming growth factor (TGF)-β, as well as Wnt and Notch signaling pathways. This entails the activation of numerous transcription factors, including ZEB, TWIST, and Snail proteins, acting as transcriptional repressors of epithelial markers, such as E-cadherin and inducers of mesenchymal markers such as vimentin. These genetic and phenotypic changes ultimately facilitate cancer cell migration. However, to successfully form distant metastases, CTCs must primarily withstand the hostile environment of circulation. This includes adaption to shear stress, avoiding being trapped by coagulation and surviving attacks of the immune system. Several applications of CTCs, from cancer diagnosis and screening to monitoring and even guided therapy, seek their way into clinical practice. This review describes the process leading to tumor metastasis, from the generation of CTCs in primary tumors to their dissemination into distant organs, as well as the importance of subtyping CTCs to improve personalized and targeted cancer therapy. Full article
(This article belongs to the Special Issue Metastasis and Tumor Cell Migration of Solid Tumors)
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28 pages, 4035 KiB  
Review
Anoikis-Associated Lung Cancer Metastasis: Mechanisms and Therapies
by Jing Wang, Zhijie Luo, Lizhu Lin, Xinbing Sui, Lili Yu, Cong Xu, Ruonan Zhang, Ziming Zhao, Qianru Zhu, Bo An, Qiao Wang, Bi Chen, Elaine Lai-Han Leung and Qibiao Wu
Cancers 2022, 14(19), 4791; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194791 - 30 Sep 2022
Cited by 32 | Viewed by 4408
Abstract
Tumor metastasis occurs in lung cancer, resulting in tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats tumor metastasis; it inhibits the escape of tumor cells from the native extracellular matrix to other organs. Deciphering the regulators and mechanisms [...] Read more.
Tumor metastasis occurs in lung cancer, resulting in tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats tumor metastasis; it inhibits the escape of tumor cells from the native extracellular matrix to other organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat lung cancer. Several natural and synthetic products exhibit the pro-anoikis potential in lung cancer cells and in vivo models. These products include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, and carbenoxolone. This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis. Full article
(This article belongs to the Special Issue Metastasis and Tumor Cell Migration of Solid Tumors)
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