Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer

Abstract Introduction Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) is a core...

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Main Authors: Rie Shibata, Hirotaka Konishi, Tomohiro Arita, Yusuke Yamamoto, Hayato Matsuda, Taiga Yamamoto, Takuma Ohashi, Hiroki Shimizu, Shuhei Komatsu, Atsushi Shiozaki, Takeshi Kubota, Hitoshi Fujiwara, Eigo Otsuji
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70212
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author Rie Shibata
Hirotaka Konishi
Tomohiro Arita
Yusuke Yamamoto
Hayato Matsuda
Taiga Yamamoto
Takuma Ohashi
Hiroki Shimizu
Shuhei Komatsu
Atsushi Shiozaki
Takeshi Kubota
Hitoshi Fujiwara
Eigo Otsuji
author_facet Rie Shibata
Hirotaka Konishi
Tomohiro Arita
Yusuke Yamamoto
Hayato Matsuda
Taiga Yamamoto
Takuma Ohashi
Hiroki Shimizu
Shuhei Komatsu
Atsushi Shiozaki
Takeshi Kubota
Hitoshi Fujiwara
Eigo Otsuji
author_sort Rie Shibata
collection DOAJ
description Abstract Introduction Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC. Methods We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated. Results The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence‐free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion. Conclusions These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample‐based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target.
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spelling doaj-art-ea82effada5a4f03af9274e5ce3e35ff2025-08-20T02:01:29ZengWileyCancer Medicine2045-76342024-09-011318n/an/a10.1002/cam4.70212Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancerRie Shibata0Hirotaka Konishi1Tomohiro Arita2Yusuke Yamamoto3Hayato Matsuda4Taiga Yamamoto5Takuma Ohashi6Hiroki Shimizu7Shuhei Komatsu8Atsushi Shiozaki9Takeshi Kubota10Hitoshi Fujiwara11Eigo Otsuji12Division of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanDivision of Digestive Surgery, Department of Surgery Kyoto Prefectural University of Medicine Kyoto JapanAbstract Introduction Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC. Methods We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated. Results The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence‐free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion. Conclusions These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample‐based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target.https://doi.org/10.1002/cam4.70212esophageal cancerglycocalyxglypican‐1GPC1liquid biopsy
spellingShingle Rie Shibata
Hirotaka Konishi
Tomohiro Arita
Yusuke Yamamoto
Hayato Matsuda
Taiga Yamamoto
Takuma Ohashi
Hiroki Shimizu
Shuhei Komatsu
Atsushi Shiozaki
Takeshi Kubota
Hitoshi Fujiwara
Eigo Otsuji
Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer
Cancer Medicine
esophageal cancer
glycocalyx
glypican‐1
GPC1
liquid biopsy
title Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer
title_full Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer
title_fullStr Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer
title_full_unstemmed Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer
title_short Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer
title_sort extracellular glypican 1 affects tumor progression and prognosis in esophageal cancer
topic esophageal cancer
glycocalyx
glypican‐1
GPC1
liquid biopsy
url https://doi.org/10.1002/cam4.70212
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