Abstract 920: Migratory cancer side population cells induces stem cell altruism in bone marrow mesenchymal stem cells to resist therapy, and enhance tumorigenic potential of non-tumorigenic cells
Bibliographic record
Abstract
Abstract Stem cell may exhibit altruistic behavior that may benefit cancer cells. We recently demonstrated altruistic phenotype in human embryonic stem cells (Das B et al. Stem Cells 2012). The phenotype exhibited reversible induction of high HIF-2alpha and low p53 expression, associated with high glutathione secretion. We speculated that cancer stem cell might induce a similar altruistic phenotype in human bone marrow (BM) derived stem cells (hematopoietic, mesenchymal and endothelial cells). The altruistic reprogrammed BM cells may then facilitate tumor growth, as well as resist the toxicity of oxidative-stress inducing anti-cancer agents. To investigate this possibility, we have obtained conditioned media (CM) from migratory side-population (SPm) and non-SP cells of a diverse panel of tumors including epithelial tumors. The SPm cells exhibit very high tumorigenic capacity (Das B et al, Stem Cell, 2008). The CM was added to in vitro bone marrow (BM) derived CD133+ cells that contain hematopoietic, endothelial, and mesenchymal stem cells. We found that SPm derived CM (henceforth known as SPm-CM) treatment increased the self-renewal capacity of CD271+/CD45- BM-MSCs. Importantly, the reprogrammed CD271+ BM-MSCs (henceforth known as R-MSCs) phenotype exhibited enhanced stemness reprogramming, a cytoprotective mechanism associated with stem cell altruism (Das B et al. Stem Cells, 2012). In contrast, the treatment with CM obtained from non-SP cells did not exhibit R-MSCs. We found that VEGF/VEGR1 autocrine signaling may be involved in R-MSCs mechanism. Importantly, the R-MSCs derived CM reprogrammed non-CSCs to CSCs, and reduced the toxicity of chemotherapy on non-SP cells. In vivo, R-MSCs derived CM, when injected to mice, exhibited mobilization of CD271+ BM-MSCs to circulation. The circulatory CD271+ BM-MSCs exhibited distinct phenotype of R-MSCs including high expression of HIF-2alpha, and VEGFR1. Finally, in human cancer patients, we identified R-MSC phenotype in the peripheral circulation. These studies suggest that cancer stem cells may exploit stem cell altruism to reprogram BM-MSCs for their own benefit. The reprogrammed BM-MSCs gene expression may have the potential as a diagnostic marker for CSC-induced stem cell altruism. Citation Format: Joyeeta Talukdar, Rashmi Bhuyan, Jaishree Garhyan, Bidisha Pal, Sora Sandhya, Sukanya Gayan, Anupam Sarma, Reza Bayat-Mokhtari, Hong Li, Jyotirmoy Phukan, Wael Tasabehji, Seema Bhuyan, Amal Ch Kataki, Rika Tsuchida, Herman Yeger, Debabrata Baishya, Bikul Das. Migratory cancer side population cells induces stem cell altruism in bone marrow mesenchymal stem cells to resist therapy, and enhance tumorigenic potential of non-tumorigenic cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 920.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".