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dc.contributor.authorReader, Jocelyn C
dc.contributor.authorFan, Cong
dc.contributor.authorOry, Eleanor Claire-Higgins
dc.contributor.authorJu, Julia
dc.contributor.authorLee, Rachel
dc.contributor.authorVitolo, Michele I
dc.contributor.authorSmith, Paige
dc.contributor.authorWu, Sulan
dc.contributor.authorChing, Mc Millan Nicol
dc.contributor.authorAsiedu, Emmanuel B
dc.contributor.authorJewell, Christopher M
dc.contributor.authorRao, Gautam G
dc.contributor.authorFulton, Amy
dc.contributor.authorWebb, Tonya J
dc.contributor.authorYang, Peixin
dc.contributor.authorSantin, Alessandro D
dc.contributor.authorHuang, Huang-Chiao
dc.contributor.authorMartin, Stuart S
dc.contributor.authorRoque, Dana M
dc.date.accessioned2022-02-17T15:36:29Z
dc.date.available2022-02-17T15:36:29Z
dc.date.issued2022-02-04
dc.identifier.urihttp://hdl.handle.net/10713/18012
dc.description.abstractBackground: 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.en_US
dc.description.urihttps://doi.org/10.3390/cancers14030800en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancersen_US
dc.subjectclear cell carcinomaen_US
dc.subjectepothiloneen_US
dc.subjectintraperitoneal chemotherapyen_US
dc.subjectixabepiloneen_US
dc.subjectmicrotentacleen_US
dc.subjectmicrotubulesen_US
dc.subjectovarian canceren_US
dc.subjectpaclitaxelen_US
dc.subjectserous carcinomaen_US
dc.subjecttaxaneen_US
dc.titleMicrotentacle Formation in Ovarian Carcinoma.en_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers14030800
dc.identifier.pmid35159067
dc.source.journaltitleCancers
dc.source.volume14
dc.source.issue3
dc.source.countrySwitzerland


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