Vascular determinants of cancer stem cell dormancy—do age and coagulation system play a role?
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The inability of tumour-initiating cancer stem cells (CSCs) to bring about a net increase in tumour mass could be described as a source of tumour dormancy. While CSCs may be intrinsically capable of driving malignant growth, to do so they require compatible surroundings of supportive cells, growth factors, adhesion molecules and energy sources (e.g. glucose and oxygen), all of which constitute what may be referred to as a 'permissive' CSC niche. However, in some circumstances, the configuration of these factors could be incompatible with CSC growth (a 'non-permissive' niche) and lead to their death or dormancy. CSCs and their niches may also differ between adult and paediatric cancers. In this regard the various facets of the tumour-vascular interface could serve as elements of the CSC niche. Indeed, transformed cells with an increased tumour-initiating capability may preferentially reside in specific zones adjacent to tumour blood vessels, or alternatively originate from poorly perfused and hypoxic areas, to which they have adapted. CSCs themselves may produce increased amounts of angiogenic factors, or rely for this on their progeny or activated host stromal cells. It is likely that 'vascular' properties of tumour-initiating cells and those of their niches may diversify and evolve with tumour progression. The emerging themes in this area include the role of vascular (and bone marrow) aging, vascular and metabolic comorbidities (e.g. atherosclerosis) and the effects of the coagulation system (both at the local and systemic levels), all of which could impact the functionality of CSCs and their niches and affect tumour growth, dormancy and formation of occult as well as overt metastases. In this article we will discuss some of the vascular properties of CSCs relevant to tumour dormancy and progression, including: (i) the role of CSCs in regulating tumour vascular supply, i.e the onset and maintenance of tumour angiogenesis; (ii) the consequences of changing vascular demand (vascular dependence) of CSC and their progeny; (iii) the interplay between CSCs and the vascular system during the process of metastasis, and especially (iv) the impact of the coagulation system on the properties of CSC and their niches. We will use the oncogene-driven expression of tissue factor (TF) in cancer cells as a paradigm in this regard, as TF represents a common denominator of several vascular processes that commonly occur in cancer, most notably coagulation and angiogenesis. In so doing we will explore the therapeutic implications of targeting TF and the coagulation system to modulate the dynamics of tumour growth and tumour dormancy.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it