Deregulated Expression of the Human Tumor Marker CEA and CEA Family Member CEACAM6 Disrupts Tissue Architecture and Blocks Colonocyte Differentiation
Why this work is in the frame
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Bibliographic record
Abstract
Human carcinoembryonic antigen (CEA) and the CEA family member CEACAM6 (formerly nonspecific cross-reacting antigen [NCA]) function in vitro, at least, as homotypic intercellular adhesion molecules and, in model systems, can block the terminal differentiation and anoikis of several different cell types. We have recently demonstrated that the increased cell surface levels of CEA and CEACAM6 in purified human colonocytes from freshly excised, well to poorly differentiated colon carcinomas are inversely correlated with the degree of cellular differentiation. Thus, deregulated expression of CEA/CEACAM6 could directly contribute to colon tumorigenesis by the inhibition of terminal differentiation and anoikis. Evidence against this view includes the common observation of increased CEA/CEACAM6 expression as normal colonocytes differentiate in their migration up colonic crypt walls. We report here the direct effects of deregulated overexpression of CEA/CEACAM6, at levels observed in colorectal carcinomas, on the differentiation of two human colonic cell lines, SW-1222 and Caco-2. Stable transfectants of both of these cell lines that constitutively express 10- to 30-fold higher cell surface levels of CEA/CEACAM6 than endogenous levels failed to polarize and differentiate into glandular structures in monolayer or 3D culture or to form colonic crypts in a tissue architecture assay in nude mice. In addition, these transfectants were found to exhibit increased tumorigenicity in nude mice. These results thus support the contention that deregulated overexpression of CEA and CEACAM6 could provide a tumorigenic contribution to colon carcinogenesis.
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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) | 0.000 | 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) | 0.000 | 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