Journal article
Aberrant expression of TMEM205 signaling promotes platinum resistance in ovarian cancer: An implication for the antitumor potential of DAP compound
Gynecologic oncology, Vol.164(1), pp.136-145
01/2022
DOI: 10.1016/j.ygyno.2021.10.076
PMID: 34756749
Abstract
TMEM205 is a novel transmembrane protein associated with platinum resistance (PR) in epithelial ovarian carcinoma (OC), however, the specific mechanisms associated with this resistance remain to be elucidated.
TMEM205 expression was evaluated in platinum-sensitive (PS) versus platinum resistant (PR) ovarian cancer cell lines and patient serum/tissues. Exosomal efflux of platinum was evaluated with inductively coupled plasma mass spectrometry (ICP-MS) after pre-treatment with small molecule inhibitors (L-2663/L-2797) of TMEM205 prior to treatment with platinum. Cytotoxicity of combination treatment was confirmed in vitro and in an in vivo model.
TMEM205 expression was 10–20 fold higher in PR compared to PS ovarian cancer cell lines, serum samples, and tissues. Co-localization with CD1B was confirmed by in-situ proximity ligation assay suggesting that TMEM205 may mediate PR via the exosomal pathway. Exosomal secretion was significantly increased 5–10 fold in PR cell lines after treatment with carboplatin compared to PS cell lines. Pre-treatment with L-2663 prior to carboplatin resulted in significantly increased intracellular concentration of fluorescently-labeled cisplatin and decreased exosomal efflux of platinum. Decreased cell survival and tumor growth in vitro and in vivo was observed when PR cells were treated with a combination of L-2663 with carboplatin compared to carboplatin alone.
TMEM205 appears to be involved in the development of PR in ovarian cancer through the exosomal efflux of platinum agents. This study provides pre-clinical evidence that TMEM205 could serve as a possible biomarker for PR as well as a therapeutic target in combination with platinum agents.
•TMEM205 and CD1B membrane proteins are highly elevated in OC tissues.•TMEM205 mediated exosome secretion associated with platinum resistance in OC.•L-2663 could effectively suppress platinum resistance in OC by inhibiting TMEM205.
Details
- Title: Subtitle
- Aberrant expression of TMEM205 signaling promotes platinum resistance in ovarian cancer: An implication for the antitumor potential of DAP compound
- Creators
- Corinne A. Calo - The Ohio State University Wexner Medical CenterBrentley Q. Smith - The Ohio State University Wexner Medical CenterKalpana Deepa Priya Dorayappan - The Ohio State University Wexner Medical CenterUksha Saini - The Ohio State University Wexner Medical CenterMichelle Lightfoot - The Ohio State University Wexner Medical CenterVincent Wagner - The Ohio State University Wexner Medical CenterDeepika Kalaiyarasan - The Ohio State University Wexner Medical CenterCasey Cosgrove - The Ohio State University Wexner Medical CenterQi-En Wang - The Ohio State UniversityG. Larry Maxwell - Inova Health SystemTamás Kálai - University of PecsPeriannan Kuppusamy - Dartmouth CollegeDavid E. Cohn - The Ohio State University Wexner Medical CenterKaruppaiyah Selvendiran - The Ohio State University Wexner Medical Center
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.164(1), pp.136-145
- DOI
- 10.1016/j.ygyno.2021.10.076
- PMID
- 34756749
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 01/2022
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984460338302771
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