Abstract B68: Characterization of microtentacle phenotype and function in ovarian carcinomas
Bibliographic record
Abstract
Abstract Ovarian carcinomas are categorized into five major histotypes, each characterized by distinct differences in grade at diagnosis, presentation with metastatic disease, and clinical responses to treatments. Microtentacles (McTNs), microtubule-based extensions of the plasma membrane, were initially described on cells of nongynecologic primaries with high metastatic potential but have not been extensively explored in ovarian carcinomas. In this study, we investigated whether ovarian cancer cells exhibit McTNs as well as the effect of microtubule-targeted drugs on ovarian cancer McTNs. We analyzed 3 immortalized ovarian surface epithelium cell lines (IOSE), 8 clear-cell (OCCC), 3 low-grade serous (LGS), and 6 high-grade serous (HGS) ovarian cancer cells for McTN phenotype, length, and number, using a novel tethering platform in which cells are suspended but stationary, allowing for analysis via confocal microscopy. Additionally, selected cell lines were also treated with microtubule-targeting agents, including paclitaxel, ixabepilone, vinblastine, and colchicine and the effects on McTN dynamics and functions were analyzed. Tubulin subtype expression and post-translational modifications (PTM) were characterized by Western blot. Unpaired t-tests were used to describe differences between McTN length and number. We observed 4 patterns of McTN expression: absent (A), symmetric-short (SS), symmetric-long (SL), and tufted (T). In some cases, multiple morphologies were observed within the same cell line. LGS and OCCC expressed fewer McTNs per cell than HSC. McTNs were shorter among OCCC compared to HGS; whereas LGS expressed a range of McTN lengths similar to those observed in HGS. We also observed differences in the expression of the PTM between the different ovarian cancer subtypes, including alterations in alpha tubulin-stabilizing modifications such as glu-tubulin and acetylated tubulin, as well as proteins involved in actin cortex stability. Increased acetylated tubulin was associated with increased McTN number and length in HGS cells. Microtubule-destabilizing drugs such as colchicine and vinblastine led to a decrease in McTN formation. Ovarian cancer metastasis typically occurs through shedding of the main tumor into the peritoneal space, and the spread of disease is the leading cause of mortality. Studying McTN function and response to chemotherapeutics allows us to improve our understanding of ovarian cancer metastasis and the effect of microtubule-targeting compounds on the spread of ovarian cancer. Citation Format: Cong (Ava) Fan, Sulan Wu, Jocelyn Reader, Eleanor Claire-Higgins Ory, Cornell Lee, McMillan Ching, Trevor Mathias, Julia Ju, Rachel Lee, Michele Vitolo, Stuart Martin, Christopher Jewell, Amy Fulton, Gautam Rao, Mark Carey, Dana M. Roque. Characterization of microtentacle phenotype and function in ovarian carcinomas [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B68.
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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) | 0.002 | 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".