Abstract 1376: Exercise alters breast cancer phenotype through distinct reductions in host-derived proinflammatory growth factor ligands.
Bibliographic record
Abstract
Abstract It is becoming increasingly recognized that host (systemic) and tumor cell release of proinflammatory growth factors are critical determinants of cancer progression and therapeutic response in patients with solid tumors. Thus, strategies that can attenuate systemic and/or tumor production of proinflammatory growth factors may offer an effective approach to improve therapeutic outcomes following a cancer diagnosis. The present study tests the central hypothesis that exercise modulates systemic levels of key growth factor ligands that, in turn, inhibit the activity of critical downstream cell signaling pathways to effectively inhibit tumor progression. To address this question, we took advantage of sera collected from a clinical trial examining the efficacy of supervised exercise training, relative to sedentary control, in patients with early or advanced solid tumors. Multiplex ELISA analysis showed that exercising patients (N=23) had significant reductions in circulating concentrations of interleukin (IL)-4, MIP1-β (macrophage inflammatory protein-1β), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and hepatocyte growth factor (HGF) in comparison with patients randomized to sedentary control (N=21). Exposure of estrogen receptor positive (ER+) and Triple-Negative (ER-/PR-/HER2-) distinct human breast cancer cell lines (MCF-7 and MDA-MB-231) to serum from exercised breast cancer patients led to marked alterations in cellular phenotype as shown by increases in proliferation, migration, and apoptosis, compared with exposure to serum from control patients. In vitro ‘add-back’ experiments using recombinant growth factors in concentrations consistent with that observed in the clinical trial, revealed that HGF produced similar alterations in tumor proliferation and apoptosis as that observed with serum from exercising patients. Co-culturing of human breast cancer cells with exercise serum and a neutralizing antibody against HGF, led to increases in proliferation and decreases in apoptosis in comparison to exercise serum alone. These results suggest that growth factor ligand deprivation may play a critical role in mediating the effects of exercise on tumor cellular phenotype. As such, our findings may provide initial insight into the potential mechanisms underlying recent observations showing higher levels of exercise correlate with more favorable disease outcomes in early breast cancer patients. More generally, this study indicates the widespread potential of exercise to modulate growth factor-driven signaling and by extension, tumor progression and possibly innate or acquired resistance to therapy. Citation Format: Oliver Glass, Brant A. Inman, Kerry S. Courneya, John R. Mackey, Erik Nelson, Zachary Hartman, Lee W. Jones. Exercise alters breast cancer phenotype through distinct reductions in host-derived proinflammatory growth factor ligands. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1376. doi:10.1158/1538-7445.AM2013-1376
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".