Growth-regulated oncogene-α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells

Mei Yin Ye, Meng Yen Chen, Ya Han Chang, Jehn Shyun Huang, Tze Ta Huang, Tung Yiu Wong, Tse Ming Hong, Yuh Ling Chen

Research output: Contribution to journalArticle

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression. Methods: We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth. Results: GRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK. Conclusion: GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

Original languageEnglish
Pages (from-to)880-886
Number of pages7
JournalJournal of Oral Pathology and Medicine
Volume47
Issue number9
DOIs
Publication statusPublished - 2018 Oct

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Oral Submucous Fibrosis
Oncogenes
Fibroblasts
Growth
Conditioned Culture Medium
Cell Movement
Squamous Cell Carcinoma
Cell Proliferation
Neoplasms
Carcinogenesis
Cytokines
CXC Chemokines
Tumor Microenvironment
MAP Kinase Signaling System
Mouth Neoplasms
Neutralizing Antibodies
Keratinocytes
Wound Healing
Agar
Actins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Oral Surgery
  • Otorhinolaryngology
  • Cancer Research
  • Periodontics

Cite this

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title = "Growth-regulated oncogene-α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells",
abstract = "Background: Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression. Methods: We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth. Results: GRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK. Conclusion: GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.",
author = "Ye, {Mei Yin} and Chen, {Meng Yen} and Chang, {Ya Han} and Huang, {Jehn Shyun} and Huang, {Tze Ta} and Wong, {Tung Yiu} and Hong, {Tse Ming} and Chen, {Yuh Ling}",
year = "2018",
month = "10",
doi = "10.1111/jop.12768",
language = "English",
volume = "47",
pages = "880--886",
journal = "Journal of Oral Pathology and Medicine",
issn = "0904-2512",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Growth-regulated oncogene-α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells

AU - Ye, Mei Yin

AU - Chen, Meng Yen

AU - Chang, Ya Han

AU - Huang, Jehn Shyun

AU - Huang, Tze Ta

AU - Wong, Tung Yiu

AU - Hong, Tse Ming

AU - Chen, Yuh Ling

PY - 2018/10

Y1 - 2018/10

N2 - Background: Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression. Methods: We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth. Results: GRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK. Conclusion: GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

AB - Background: Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression. Methods: We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth. Results: GRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK. Conclusion: GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

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U2 - 10.1111/jop.12768

DO - 10.1111/jop.12768

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JO - Journal of Oral Pathology and Medicine

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SN - 0904-2512

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