KS-EMPD-1: a novel cell line of primary extramammary Paget’s disease

Ito, Takamichi; Tanaka, Yuka; Ichiki, Toshio; Kaku-Ito, Yumiko; Nakahara, Takeshi

doi:10.1007/s13577-023-00951-1

Cited by 4 publications

(10 citation statements)

References 87 publications

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“…Cancer cell lines are essential tools to screen potential therapeutic targets of cancer, but the analysis of EMPD has been largely limited by the lack of EMPD cell lines maintainable in conventional two‐dimensional culture systems. We have recently established an EMPD cell line, KS‐EMPD‐1, 41 which allowed us to perform in vitro analyses of EMPD. Using this cell line, we here focused on the cell adhesion molecule NECTIN4 as a novel therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

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NECTIN4‐targeted antibody–drug conjugate is a potential therapeutic option for extramammary Paget disease

Tanaka,

Ito,

Murata

et al. 2024

Experimental Dermatology

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Extramammary Paget disease (EMPD) is a rare skin cancer mainly found in areas rich in apocrine sweat glands. Since the effective treatments for advanced and/or metastasized EMPD are limited, there is an urgent need to develop novel therapeutic approaches. Nectin cell adhesion molecule 4 (NECTIN4) is highly expressed in cancers and considered to be a promising therapeutic target. NECTIN4 is also expressed in EMPD, but its role and the efficacy of NECTIN4‐targeted therapy in EMPD remain unclear. This study investigated the potential of NECTIN4 as a novel therapeutic target for EMPD. NECTIN4 expression was immunohistochemically analysed in EMPD patients' primary (118 samples) and metastatic (21 samples) lesions. Using an EMPD cell line, KS‐EMPD‐1, the effects of NECTIN4 inhibition on cell proliferation and migration were investigated. NECTIN4 was expressed in primary and metastatic EMPD lesions, and the H‐score of NECTIN4 staining was significantly higher in metastatic lesions than in primary ones. Knockdown of NECTIN4 significantly inhibited cell proliferation and affected cell migration. The cytotoxic effects of NECTIN4‐targeted antibody–drug conjugate (ADC) were further evaluated, revealing a significant decrease in EMPD cell viability. In conclusion, NECTIN4 is a potential therapeutic target and NECTIN4‐targeted ADC is promising as a therapeutic option for EMPD.

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Section: Discussionmentioning

confidence: 99%

“…An EMPD cell line, KS‐EMPD‐1 (originally generated by T. Ito and colleagues 41 ), was cultured in EBM2 medium (C‐22111; Takara Bio Inc., Tokyo, Japan) supplemented with Heregulin β1 (100‐03; PeproTech, Cranbury, NJ, USA). The medium was refreshed every 2–3 days, and cells were passaged with trypsin at 80% confluence.…”

Section: Methodsmentioning

confidence: 99%

NECTIN4‐targeted antibody–drug conjugate is a potential therapeutic option for extramammary Paget disease

Tanaka,

Ito,

Murata

et al. 2024

Experimental Dermatology

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“…In this study, we immunostained a relatively large number of EMPD clinical samples and conducted several in vitro analyses using our newly established EMPD cell line, KS-EMPD-1 60 , in order to investigate the role of FOXM1 in the tumorigenesis of this disease and examine FOXM1 as a potential therapeutic target of EMPD. We found that, even in the early stages of EMPD, most cases showed strong and abundant positive expression of FOXM1, and its positivity increased with tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…A major limitation of this study is the limited number of cell lines used. However, until we established the KS-EMPD-1 cell line 60 , there was no cell line available for EMPD. Currently, KE-EMPD-1 is the only cell line available for EMPD.…”

Section: Discussionmentioning

confidence: 99%

“…However, the difficulty in establishing in vivo or in vitro models of EMPD had hampered basic research to explore the pathobiology of EMPD. We recently established a novel EMPD cell line, named KS-EMPD-1 60 . In this study, we investigated FOXM1 expression and its role in tumor proliferation and development in EMPD patients’ clinical samples and in this cell line.…”

Section: Introductionmentioning

confidence: 99%

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FOXM1: a new therapeutic target of extramammary Paget disease

Ito,

Tanaka,

Kaku-Ito

et al. 2024

Sci Rep

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Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.

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TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis

Tanegashima,

Tanaka,

Ito

et al. 2024

Experimental Dermatology

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Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, but treatments for advanced cases have limited efficacy. Trophoblast cell‐surface antigen 2 (TROP2) is a cell‐surface protein that is widely expressed in various tumours, where it exerts significant influence over critical processes such as tumour cell growth, apoptosis, migration, invasion and metastasis. Sacituzumab govitecan, an antibody‐drug conjugate (ADC) targeting TROP2, is emerging as a promising strategy for anticancer therapy. In this study, we investigated TROP2 expression in cSCC tissues from 51 patients and evaluated its function in the A431 human SCC cell line. Immunohistochemical analysis revealed TROP2 expression on the plasma membrane of cSCC tissues and A431 cells. A431 cells showed sensitivity to sacituzumab govitecan with a significant concentration‐dependent decrease in viable cell number. In addition, Knockdown of TROP2 resulted in decreased expression of cyclin D1 and BCL‐2, along with reduced cell viability. Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.

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KS-EMPD-1: a novel cell line of primary extramammary Paget’s disease

Cited by 4 publications

References 87 publications

NECTIN4‐targeted antibody–drug conjugate is a potential therapeutic option for extramammary Paget disease

NECTIN4‐targeted antibody–drug conjugate is a potential therapeutic option for extramammary Paget disease

FOXM1: a new therapeutic target of extramammary Paget disease

TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis

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