Insights into mechanisms of tumor dissemination from circulating tumor cell lines of small cell lung cancer

Hamilton, Gerhard; Rath, Barbara H.

doi:10.20517/2394-4722.2016.57

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…All definitions are based on the local levels of oxygen and glucose, implying respectively the stop (necrosis) or a reduction (quiescence) in the glycolysis, and consequently in the regeneration of ATP. The second element is the experimentally observed shedding of cells from the surface of tumor spheroids [5,48,49], similar to what happens in a real tumoral mass disseminating circulating cancer cells [50].…”

Section: Simulation Of Spheroid Growth Saturationmentioning

confidence: 69%

Agent-based model of multicellular tumor spheroid evolution including cell metabolism

Cleri

2019

Eur. Phys. J. E

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Computational models aiming at the spatio-temporal description of cancer evolution are a suitable framework for testing biological hypotheses from experimental data, and generating new ones. Building on our recent work [J Theor Biol 389, 146-158 (2016)] we develop a 3D agent-based model, capable of tracking hundreds of thousands of interacting cells, over time scales ranging from seconds to years. Cell dynamics is driven by a Monte Carlo solver, incorporating partial differential equations to describe chemical pathways and the activation/repression of "genes", leading to the up-or down-regulation of specific cell markers. Each cell-agent of different kind (stem, cancer, stromal etc.) runs through its cycle, undergoes division, can exit to a dormant, senescent, necrotic state, or apoptosis, according to the inputs from their systemic network. The basic network at this stage describes glucose/oxygen/ATP cycling, and can be readily extended to cancer-cell specific markers. Eventual accumulation of chemical/radiation damage to each cell's DNA is described by a Markov chain of internal states, and by a damage-repair network, whose evolution is linked to the cell systemic network. Aimed at a direct comparison with experiments of tumorsphere growth from stem cells, the present model will allow to quantitatively study the role of transcription factors involved in the reprogramming and variable radio-resistance of simulated cancer-stem cells, evolving in a realistic computer simulation of a growing multicellular tumorsphere.

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Section: Simulation Of Spheroid Growth Saturationmentioning

confidence: 69%

Agent-based model of multicellular tumor spheroid evolution including cell metabolism

Cleri

2019

Eur. Phys. J. E

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“…We have shown previously that SCLC CTCs form large aggregates, termed tumorospheres, spontaneously in tissue culture and that such spheroids exhibit significantly higher levels of resistance to chemotherapeutics as compared to single cell suspensions [7] . Such tumorospheres may not exist in the circulation, but they form in capillaries prior to extravasation and generation of metastases [13] . Furthermore, our collection of SCLC CTCs exhibit shedding of large quantities of cellular fragments in the presence of intact tumor cells, which can then be cultivated for unlimited passages.…”

Section: Discussionmentioning

confidence: 99%

Protection of small-cell lung cancer circulating tumor cells by cellular fragmentation

Rath¹,

Plangger²,

Moser³

et al. 2020

JCMT

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Aim: Small-cell lung cancer (SCLC) disseminates aggressively and may exhibit high chemoresistance and poor survival rates. In this study, we aimed to investigate a new mechanism of drug resistance for SCLC circulating tumor cells (CTCs). Methods: SCLC CTC cell lines (n = 4) which shed cellular fragments (MAT), as demonstrated by light and scanning electron microscopy, are compared to permanent SCLC lines. Selected proteins are detected by proteome arrays and the functional impact of MAT is studied using cytotoxicity tests involving cisplatin and Topotecan. Results: The SCLC CTC lines revealed layers of attached cellular fragments with a range of decreasing sizes from intact cells (approximately 12 µm) down to small debris (approximately 2 µm) which are not detectable in permanent SCLC lines. Intact SCLC CTC clusters represent cores of these fragment-coated spheroids. Proteome profiling of MAT revealed a protein pattern similar to intact cells. Chemosensitivity tests employing SCLC and SCLC CTC lines with chemotherapeutics used in therapy of SCLC demonstrated an inhibitory activity of MAT on the resulting cytotoxicity. Conclusion: Generation of cell-associated debris by SCLC CTCs offers protective effects against cytotoxic drugs, representing a novel mechanism allowing survival of SCLC CTCs in patients.

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“…For a cancer to metastasise, it requires a series of key dynamic and interconnected steps, simplified in the paradigm of: genetic mutation, cell proliferation, angiogenesis, intravasation, extravasation and finally proliferation at the end organ parenchyma 4 – 7 . Animal models suggest that for one gram of tumour, 4.6 × 10 6 tumour cells are shed into the circulation every 24 h. With less than 0.01% of these cells forming secondary tumour growths, most of these cells are rapidly destroyed by the immune system, before they can adhere to distant capillary endothelial layers 2 , 8 .…”

Section: Introductionmentioning

confidence: 99%

A pilot study to investigate if the mesenteric circumferential location of colon cancer affects survival when compared to the anti-mesenteric side

Horwell

Sagias

2021

Sci Rep

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Colorectal cancer is a leading cause of death in the western world. The main datum that is employed to guide treatment and prognosis are related to the pathological stage and the genetics of the cancer. Recent electron-microscopic study of the colonic border has suggested a difference between the micro-anatomy of the mesenteric border11, compared to the anti-mesenteric. With colorectal cancer increasing in incidence, the more information that we can employ to guide and tailor patient centred management, the better. A pilot study to test the hypothesis that the circumferential location on the colonic wall, mesenteric or anti-mesenteric, has an impact on the mortality rate associated with right-sided colon cancer. All patients undergoing a right hemicolectomy for non-metastatic adenocarcinoma between 2010 and 2013 were included (155 patients in total). T and N stage were recorded. There was no statistical difference between the groups for age or sex. Survival rates were then calculated according to the location of the cancer and analysed using Kaplan–Meir survival calculations. 100 patients were included in the final analysis. 90 patients had cancer on the antimesenteric border. The T and N stage were not statistically different between the two groups. The mean all-cause survival was 44 months for the mesenteric group and 77 for the antimesenteric (P = 0.002). Disease free survival was 41 versus 60 months accordingly (P = 0.021). Mesenteric cancer appears to have a shorter survival time, and may be a good candidate for future prognostication and treatment algorithms. Interesting this survival difference is observed even with a lower average T stage in the mesenteric group. The histological recording of the circumferential location is a zero cost and easy metric to record.

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Insights into mechanisms of tumor dissemination from circulating tumor cell lines of small cell lung cancer

Cited by 5 publications

References 43 publications

Agent-based model of multicellular tumor spheroid evolution including cell metabolism

Agent-based model of multicellular tumor spheroid evolution including cell metabolism

Protection of small-cell lung cancer circulating tumor cells by cellular fragmentation

A pilot study to investigate if the mesenteric circumferential location of colon cancer affects survival when compared to the anti-mesenteric side

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