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    Microtentacle Formation in Ovarian Carcinoma.

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    Author
    Reader, Jocelyn C
    Fan, Cong
    Ory, Eleanor Claire-Higgins
    Ju, Julia
    Lee, Rachel
    Vitolo, Michele I
    Smith, Paige
    Wu, Sulan
    Ching, Mc Millan Nicol
    Asiedu, Emmanuel B
    Jewell, Christopher M
    Rao, Gautam G
    Fulton, Amy
    Webb, Tonya J
    Yang, Peixin
    Santin, Alessandro D
    Huang, Huang-Chiao
    Martin, Stuart S
    Roque, Dana M
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    Date
    2022-02-04
    Journal
    Cancers
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.3390/cancers14030800
    Abstract
    Background: The development of chemoresistance to paclitaxel and carboplatin represents a major therapeutic challenge in ovarian cancer, a disease frequently characterized by malignant ascites and extrapelvic metastasis. Microtentacles (McTNs) are tubulin-based projections observed in detached breast cancer cells. In this study, we investigated whether ovarian cancers exhibit McTNs and characterized McTN biology. Methods: We used an established lipid-tethering mechanism to suspend and image individual cancer cells. We queried a panel of immortalized serous (OSC) and clear cell (OCCC) cell lines as well as freshly procured ascites and human ovarian surface epithelium (HOSE). We assessed by Western blot β-tubulin isotype, α-tubulin post-translational modifications and actin regulatory proteins in attached/detached states. We studied clustering in suspended conditions. Effects of treatment with microtubule depolymerizing and stabilizing drugs were described. Results: Among cell lines, up to 30% of cells expressed McTNs. Four McTN morphologies (absent, symmetric-short, symmetric-long, tufted) were observed in immortalized cultures as well as ascites. McTN number/length varied with histology according to metastatic potential. Most OCCC overexpressed class III ß-tubulin. OCCC/OSC cell lines exhibited a trend towards more microtubule-stabilizing post-translational modifications of α-tubulin relative to HOSE. Microtubule depolymerizing drugs decreased the number/length of McTNs, confirming that McTNs are composed of tubulin. Cells that failed to form McTNs demonstrated differential expression of α-tubulin- and actin-regulating proteins relative to cells that form McTNs. Cluster formation is more susceptible to microtubule targeting agents in cells that form McTNs, suggesting a role for McTNs in aggregation. Conclusions: McTNs likely participate in key aspects of ovarian cancer metastasis. McTNs represent a new therapeutic target for this disease that could refine therapies, including intraperitoneal drug delivery.
    Keyword
    clear cell carcinoma
    epothilone
    intraperitoneal chemotherapy
    ixabepilone
    microtentacle
    microtubules
    ovarian cancer
    paclitaxel
    serous carcinoma
    taxane
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18012
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers14030800
    Scopus Count
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