Microtentacle Formation in Ovarian Carcinoma

Jocelyn C. Reader; Cong Fan; Eleanor Claire-Higgins Ory; Julia Ju; Rachel Lee; Michele I. Vitolo; Paige Smith; Sulan Wu; Mc Millan Nicol Ching; Emmanuel B. Asiedu; Christopher M. Jewell; Gautam G. Rao; Amy Fulton; Tonya J. Webb; Peixin Yang; Alessandro D. Santin; Huang-Chiao Huang; Stuart S. Martin; Dana M. Roque

doi:10.3390/cancers14030800

Cancers (Feb 2022)

Microtentacle Formation in Ovarian Carcinoma

Jocelyn C. Reader,
Cong Fan,
Eleanor Claire-Higgins Ory,
Julia Ju,
Rachel Lee,
Michele I. Vitolo,
Paige Smith,
Sulan Wu,
Mc Millan Nicol Ching,
Emmanuel B. Asiedu,
Christopher M. Jewell,
Gautam G. Rao,
Amy Fulton,
Tonya J. Webb,
Peixin Yang,
Alessandro D. Santin,
Huang-Chiao Huang,
Stuart S. Martin,
Dana M. Roque

Affiliations

Jocelyn C. Reader: Division of Gynecologic Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Cong Fan: Division of Gynecologic Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Eleanor Claire-Higgins Ory: Department of Physiology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Julia Ju: Department of Physiology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Rachel Lee: Department of Physiology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Michele I. Vitolo: Department of Pharmacology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Paige Smith: Division of Gynecologic Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Sulan Wu: Department of Chemistry and Biochemistry, Oberlin College, Oberlin, OH 44074, USA
Mc Millan Nicol Ching: Division of Gynecologic Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Emmanuel B. Asiedu: Department of Microbiology and Immunology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Christopher M. Jewell: Fischell Department of Bioengineering, University of Maryland College Park, College Park, MD 20742, USA
Gautam G. Rao: Division of Gynecologic Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Amy Fulton: Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA
Tonya J. Webb: Department of Microbiology and Immunology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Peixin Yang: Department of Obstetrics, Gynecology & Reproductive Sciences and Biochemistry & Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Alessandro D. Santin: Division of Gynecologic Oncology, Smilow Cancer Center, Yale University, New Haven, CT 06520, USA
Huang-Chiao Huang: Fischell Department of Bioengineering, University of Maryland College Park, College Park, MD 20742, USA
Stuart S. Martin: Department of Pharmacology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Dana M. Roque: Division of Gynecologic Oncology, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA

DOI: https://doi.org/10.3390/cancers14030800
Journal volume & issue: Vol. 14, no. 3
p. 800

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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