The plasticity of germ cell cancers and its dependence on the cellular microenvironment

Nettersheim, Daniel; Schorle, Hubert

doi:10.1111/jcmm.13082

Cited by 25 publications

(26 citation statements)

References 51 publications

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“…Among these types of tumours, seminomas are considered the default developmental pathway of germ cell neoplasia in situ cells and maintain most of the molecular and biochemical features of foetal germ cells. The importance of the microenvironment for cell behaviour and, consequently, the possible onset, development and progression of seminoma lesions has been highlighted in several studies 29 . In addition, the TCam-2 cell line, which is, as previously mentioned, a seminoma cell model, displays extraordinary versatility and plasticity.…”

Section: Discussionmentioning

confidence: 99%

Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity

Morabito

Guarnieri

Catizone

et al. 2017

Sci Rep

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The effects of microgravity on functions of the human body are well described, including alterations in the male and female reproductive systems. In the present study, TCam-2 cells, which are considered a good model of mitotically active male germ cells, were used to investigate intracellular signalling and cell metabolism during exposure to simulated microgravity, a condition that affects cell shape and cytoskeletal architecture. After a 24 hour exposure to simulated microgravity, TCam-2 cells showed 1) a decreased proliferation rate and a delay in cell cycle progression, 2) increased anaerobic metabolism accompanied by increased levels of intracellular Ca2+, reactive oxygen species and superoxide anion and modifications in mitochondrial morphology. Interestingly, all these events were transient and were no longer evident after 48 hours of exposure. The presence of antioxidants prevented not only the effects described above but also the modifications in cytoskeletal architecture and the activation of the autophagy process induced by simulated microgravity. In conclusion, in the TCam-2 cell model, simulated microgravity activated the oxidative machinery, triggering transient macroscopic cell events, such as a reduction in the proliferation rate, changes in cytoskeleton-driven shape and autophagy activation.

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Section: Discussionmentioning

confidence: 99%

Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity

Morabito

Guarnieri

Catizone

et al. 2017

Sci Rep

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“…Solid tumors are more than just a lump of cancer cells. Beside stromal cells, non-cellular components of the TM include the ECM and soluble growth factors [ 93 , 94 , 95 , 96 , 97 , 98 ]. The interaction between cells and their respective microenvironment is key for cellular growth and the maintenance of homeostasis.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

346

330

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Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.

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“…TGF-β1, together with EGF and FGF4, synergistically contribute to differentiation of seminoma cells into the mixed non-seminoma-like cell type [172]. Since seminomas naturally progress into non-seminomas, this may suggest that TGF-β stimulates the progression of testicular tumors [173]. Furthermore TGF-β-induced signaling stimulates proliferation of TCam-2 seminoma cells [170].…”

Section: Testicular Cancermentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

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The plasticity of germ cell cancers and its dependence on the cellular microenvironment

Cited by 25 publications

References 51 publications

Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity

Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

TGF-β and microRNA Interplay in Genitourinary Cancers

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