The bidirectional tumor - mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Kansy, Benjamin; Dissmann, P.; Hemeda, Hatim; Bruderek, Kirsten; Westerkamp, Anna M; Jagalski, Vivien; Schuler, Patrick J.; Kansy, Katinka; Lang, Stephan; Dumitru, Claudia A.; Brandau, Sven

doi:10.1186/scrt484

Cited by 60 publications

(42 citation statements)

References 44 publications

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“…Such heterogenic functionality was also discussed in vivo with EpCAM-positive subsets of tumor-initiating cells (cancer stem cells) in patient ovarian cancer ascites also carrying markers of cancer-associated fibroblasts [44]. Other in vivo studies demonstrated crosstalk of MSC with tumor cells and promotion of tumor growth in patients with head and neck cancer, whereby MSC isolated from these patient tumors constitutively produced high levels of IL-6, IL-8, and stromal cell-derived factor (SDF)-1a [45]. In addition, co-transplantation of human adipose tissue-derived MSC with MDA-MB-231 breast cancer cells exhibited partial EMT and was associated with development of tumor xenograft metastases to multiple mouse organs [46].…”

Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stroma/Stem Cells Exchange Membrane Proteins and Alter Functionality During Interaction with Different Tumor Cell Lines

Yang

Otte

Hass

2015

Stem Cells and Development

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To analyze effects of cellular interaction between human mesenchymal stroma/stem cells (MSC) and different cancer cells, direct co-cultures were performed and revealed significant growth stimulation of the tumor populations and a variety of protein exchanges. More than 90% of MCF-7 and primary human HBCEC699 breast cancer cells as well as NIH:OVCAR-3 ovarian adenocarcinoma cells acquired CD90 proteins during MSC co-culture, respectively. Furthermore, SK-OV-3 ovarian cancer cells progressively elevated CD105 and CD90 proteins in co-culture with MSC. Primary small cell hypercalcemic ovarian carcinoma cells (SCCOHT-1) demonstrated undetectable levels of CD73 and CD105; however, both proteins were significantly increased in the presence of MSC. This co-culture-mediated protein induction was also observed at transcriptional levels and changed functionality of SCCOHT-1 cells by an acquired capability to metabolize 5¢cAMP. Moreover, exchange between tumor cells and MSC worked bidirectional, as undetectable expression of epithelial cell adhesion molecule (EpCAM) in MSC significantly increased after co-culture with SK-OV-3 or NIH:OVCAR-3 cells. In addition, a small population of chimeric/hybrid cells appeared in each MSC/tumor cell co-culture by spontaneous cell fusion. Immune fluorescence demonstrated nanotube structures and exosomes between MSC and tumor cells, whereas cytochalasin-D partially abolished the intercellular protein transfer. More detailed functional analysis of FACS-separated MSC and NIH:OVCAR-3 cells after co-culture revealed the acquisition of epithelial cell-specific properties by MSC, including increased gene expression for cytokeratins and epithelial-like differentiation factors. Vice versa, a variety of transcriptional regulatory genes were downmodulated in NIH:OVCAR-3 cells after co-culture with MSC. Together, these mutual cellular interactions contributed to functional alterations in MSC and tumor cells.

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Section: Discussionmentioning

confidence: 99%

Human Mesenchymal Stroma/Stem Cells Exchange Membrane Proteins and Alter Functionality During Interaction with Different Tumor Cell Lines

Yang

Otte

Hass

2015

Stem Cells and Development

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“…CAF bzw. mesenchymale Stromazellen sind wichtige Komponenten des Tumormilieus, da sie das Gerüst für das Tumorwachstum bilden [14]. Über Sekretion von Zytound Chemokinen wie CXCL12 oder CCL5 werden Tumorwachstum sowie Metastasierung gefördert.…”

Section: Immuntherapie S Stimulation Der Immunantwortunclassified

Immuntherapie bei Kopf-Hals-Karzinomen

Kansy

Hussain

Mattheis

et al. 2015

HNO

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The physiological immune response to malignant cells is based on the interaction of antigen-presenting cells, such as dendritic cells and macrophages, with T and B lymphocytes. CD8(+) effector and natural killer cells are primarily responsible for tumor cell lysis. Tumor cells exploit several mechanisms to influence the body's immune system and promote development and progress of solid head and neck malignancies. Via regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and cancer-associated fibroblasts, tumor cells promote development of suppressive signaling pathways that enable tumor progression. Novel immune therapeutics aim to influence these signaling pathways. Current studies are investigating agents which influence immune-stimulating or immune-suppressive cytokines, as well as drug-based Toll-like receptor activation and vaccination in head and neck cancer. Development of monoclonal antibodies allows for direct and highly specific binding of therapeutics to cell receptors - recently discovered immune checkpoint receptors are particularly intriguing targets. Monoclonal antibodies directed specifically toward T cell-stimulating receptors such as CD28 and CD134, or immunosuppressive receptors CTLA-4 and PD-1, are currently under investigation and have shown promising results.

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“…MSC are recruited by the cancer cells into the tumor site from either the bone marrow or from adjacent tissues, and become an integral cellular component of the TME where they modulate tumor progression [8][9][10][11]. MSC tropism into tumor sites is mediated by a combination of extrinsic signals together with secretion of chemokines, cytokines and growth factors secreted by cells of the TME [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Reciprocal Reprogramming of Cancer Cells and Associated Mesenchymal Stem Cells in Gastric Cancer

et al. 2018

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The interactions of cancer stem cells (CSCs) within the tumor microenvironment (TME), contribute to the overall phenomenon of intratumoral heterogeneity, which also involve CSC interactions with noncancer stromal cells. Comprehensive understanding of the tumorigenesis process requires elucidating the coordinated gene expression between cancer and tumor stromal cells for each tumor. We show that human gastric cancer cells (GSC1) subvert gene expression and cytokine production by mesenchymal stem cells (GSC‐MSC), thus promoting tumor progression. Using mixed composition of human tumor xenografts, organotypic culture, and in vitro assays, we demonstrate GSC1‐mediated specific reprogramming of “naïve” MSC into specialized tumor associated MSC equipped with a tumor‐promoting phenotype. Although paracrine effect of GSC‐MSC or primed‐MSC is sufficient to enable 2D growth of GSC1, cell–cell interaction with GSC‐MSC is necessary for 3D growth and in vivo tumor formation. At both the transcriptional and at the protein level, RNA‐Seq and proteome analyses, respectively, revealed increased R‐spondin expression in primed‐MSC, and paracrine and juxtacrine mediated elevation of Lgr5 expression in GSC1, suggesting GSC‐MSC‐mediated support of cancer stemness in GSC1. CSC properties are sustained in vivo through the interplay between GSC1 and GSC‐MSC, activating the R‐spondin/Lgr5 axis and WNT/β‐catenin signaling pathway. β‐Catenin+ cell clusters show β‐catenin nuclear localization, indicating the activation of the WNT/β‐catenin signaling pathway in these cells. The β‐catenin+ cluster of cells overlap the Lgr5+ cells, however, not all Lgr5+ cells express β‐catenin. A predominant means to sustain the CSC contribution to tumor progression appears to be subversion of MSC in the TME by cancer cells. Stem Cells 2018 Stem Cells 2019;37:176–189

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The bidirectional tumor - mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Cited by 60 publications

References 44 publications

Human Mesenchymal Stroma/Stem Cells Exchange Membrane Proteins and Alter Functionality During Interaction with Different Tumor Cell Lines

Human Mesenchymal Stroma/Stem Cells Exchange Membrane Proteins and Alter Functionality During Interaction with Different Tumor Cell Lines

Immuntherapie bei Kopf-Hals-Karzinomen

Reciprocal Reprogramming of Cancer Cells and Associated Mesenchymal Stem Cells in Gastric Cancer

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