Abstract 2467: Connexin43 reduces melanoma growth within a keratinocyte microenvironment and during tumorigenesis <i>in vivo</i>
Bibliographic record
Abstract
Abstract Gap junctions formed from connexins (Cx) have been reported to regulate proliferation, differentiation and apoptosis through formation of intercellular channels between opposing cells. Interestingly, connexins have been identified as tumor suppressors and enhancers, a distinction dependent on the type and stage of disease. In melanomas, the role of connexins during cancer onset and progression remains unclear. In the current study, we hypothesize that expression of Cx26 and Cx43 in BL6 mouse melanomas will increase gap junctional intercellular communication (GJIC) thereby decrease their tumorigenic properties. Western blots, immunofluorescence and dye coupling studies revealed that BL6 cells express low levels of Cx26 , Cx43 and are poorly coupled. When cells were engineered to express Cx26 or Cx43, dye transfer studies revealed that both Cx26- and Cx43-expressing cells were highly coupled. Interestingly, when these connexin-rich melanomas were co-cultured with Cx43-rich keratinocytes, melanoma microtumors remained functionally isolated and failed to couple to surrounding keratinocytes. Growth curve studies revealed that exogenous Cx43, but not Cx26, significantly reduced total cell numbers; that was primarily due to reduced cell proliferation. Furthermore, Cx43 expression significantly reduced anchorage-independent growth compared to controls, however, migration remained unaffected. Additionally, Cx43-expressing melanoma cells displayed a reduction in growth when co-cultured with keratinocytes, despite a lack of heterocellular GJIC. Finally, when grown in in vivo avian embryo model, primary tumor weight was reduced in tumor cells expressing Cx43 , but not in Cx26-expressing melanomas , as compared to controls. Overall, our results would suggest that Cx43 is a potent tumor suppressor in melanomas. Supported by the Canadian Institute of Health Research to DWL. Citation Format: Qing C. Shao, Mark Jake Ableser, Silvia Penuela, Dale W. Laird. Connexin43 reduces melanoma growth within a keratinocyte microenvironment and during tumorigenesis in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2467. doi:10.1158/1538-7445.AM2014-2467
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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".