Abstract 1928: The lung microenvironment promotes stem-like phenotype and behavior of breast cancer cells
Bibliographic record
Abstract
Abstract Ninety percent of breast cancer-related mortalities result from metastasis, a process whereby the primary tumour disseminates and targets distant secondary organs. We have previously demonstrated that stem-like breast cancer cells expressing high levels of aldehyde dehydrogenase (ALDH) and CD44 are critical for metastasis. These ALDHhiCD44+ cells preferentially migrate and/or metastasize to the lung and bone microenvironments, where secondary tumours can severely impede organ function. However, the specific role of the lung and bone marrow (BM) microenvironments in supporting and/or promoting metastasis of ALDHhiCD44+ cells remains poorly understood, and this is the purpose of the current study. Using a 2D ex vivo model, lung and bone marrow (BM) conditioned media (CM) enriched in tissue-specific soluble proteins were generated from murine tissues and utilized in cell culture to assess their ability to influence the stem-like phenotype and behavior of MDA-MB-468 human breast cancer cells. Exposure to lung-CM promoted the generation of a viable, non-adherent (“floating”) breast cancer cell subpopulation that was not observed in response to BM-CM or basal media (p<0.05). Phenotypic analysis by flow cytometry and gene expression analysis by RT-qPCR revealed notable differences in ALDH/CD44 phenotype in whole cell populations, adherent subpopulations, and/or non-adherent subpopulations in response to 72 hour exposure to lung-CM relative to basal media. In particular, the non-adherent breast cancer cell subpopulation generated in response to lung-CM demonstrated increased CD44 and ALDH1A3 gene expression and decreased ALDH1A1 gene expression relative to the adherent subpopulation (p<0.05). No significant phenotypic or gene expression differences were observed in MDA-MB-468 breast cancer cells in response to BM-CM. Taken together with our previous studies, these findings suggest that while both the lung and bone microenvironments support breast cancer cells with a pre-existing ALDHhiCD44+ phenotype, the lung microenvironment may additionally help to even further promote stem-like phenotype and behavior in the secondary metastatic site. Ongoing studies are aimed at elucidating the mechanisms by which aggressive ALDHhiCD44+ breast cancer cells interact with and/or are influenced by the lung microenvironment during metastatic progression. Citation Format: Ashkan Sadri, Alison L. Allan. The lung microenvironment promotes stem-like phenotype and behavior of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1928. doi:10.1158/1538-7445.AM2017-1928
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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) | 0.005 | 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".