Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model

Tobe-Nishimoto, Ayano; Morita, Yoshihiro; Nishimura, Junya; Kitahira, Yukiko; Takayama, Shun; Kishimoto, Satoko; Matsumiya-Matsumoto, Yuka; Matsunaga, Kazuhide; Imai, Tomoaki; Uzawa, Narikazu

doi:https://doi.org/10.1007/s10585-024-10306-1

Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model

Tobe-Nishimoto, Ayano; Morita, Yoshihiro; Nishimura, Junya et al.

Clinical and Experimental Metastasis, 2024, 41(6), 891-908

Number of Access:1,083（2025-07-22 20:36 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98110

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Title	Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model
Creator	CreatorName Tobe-Nishimoto, Ayano
	NRID 1000030590517 1000030590517 researchmap permalink yoshi197 yoshi197 Scopus Author ID 16069264600 16069264600 CreatorName Morita, Yoshihiro
	CreatorName Nishimura, Junya
	CreatorName Kitahira, Yukiko
	CreatorName Takayama, Shun
	NRID 1000070912228 1000070912228 researchmap permalink 10_12 10_12 CreatorName Kishimoto, Satoko
	NRID 1000080817023 1000080817023 researchmap permalink y.m.2941 y.m.2941 CreatorName Matsumiya-Matsumoto, Yuka
	NRID 1000080368323 1000080368323 researchmap permalink kazuhide kazuhide Scopus Author ID 7202702921 7202702921 CreatorName Matsunaga, Kazuhide
	NRID 1000080599598 1000080599598 researchmap permalink 67101 67101 CreatorName Imai, Tomoaki
	NRID 1000030345285 1000030345285 researchmap permalink read0212957 read0212957 Scopus Author ID 6603144046 6603144046 CreatorName Uzawa, Narikazu
Subject	Epithelial-mesenchymal transition
	Inflammatory cytokine
	Oral cancer
	Syngeneic mouse oral cancer model
	Tumor microenvironment
Description	The version of record of this article, first published in Clinical and Experimental Metastasis, is available online at Publisher’s website: https://doi.org/10.1007/s10585-024-10306-1.
Abstract	The process of cervical lymph node metastasis is dependent on the phenotype of the tumor cells and their interaction with the host microenvironment and immune system; conventional research methods that focus exclusively on tumor cells are limited in their ability to elucidate the metastatic mechanism. In cancer tissues, a specialized environment called the tumor microenvironment (TME) is established around tumor cells, and inflammation in the TME has been reported to be closely associated with the development and progression of many types of cancer and with the response to anticancer therapy. In this study, to elucidate the mechanism of metastasis establishment, including the TME, in the cervical lymph node metastasis of oral cancer, we established a mouse-derived oral squamous cell carcinoma cervical lymph node highly metastatic cell line and generated a syngeneic orthotopic transplantation mouse model. In the established highly metastatic cells, epithelial-mesenchymal transition (EMT) induction was enhanced compared to that in parental cells. In the syngeneic mouse model, lymph node metastasis was observed more frequently in tumors of highly metastatic cells than in parental cells, and Cyclooxygenase-2 (COX-2) expression and lymphatic vessels in primary tumor tissues were increased, suggesting that this model is highly useful. Moreover, in the established highly metastatic cells, EMT induction was enhanced compared to that in the parent cell line, and CCL5 and IL-6 secreted during inflammation further enhanced EMT induction in cancer cells. This suggests the possibility of a synergistic effect between EMT induction and inflammation. This model, which allows for the use of two types of cells with different metastatic and tumor growth potentials, is very useful for oral cancer research involving the interaction between cancer cells and the TME in tumor tissues and for further searching for new therapeutic agents.
Publisher	Springer Science and Business Media B.V.
Source Title	Clinical and Experimental Metastasis
Volume (Issue)	41(6)
Page	891-908
Date of Issued	2024-08-10
Language	English
Handle URL	https://hdl.handle.net/11094/98110
PISSN	02620898
eISSN	15737276
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s10585-024-10306-1
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Clinical and Experimental Metastasis. 2024, 41(6), p. 891-908
DC.title	Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model
DC.creator	Tobe-Nishimoto, Ayano
	Morita, Yoshihiro
	Nishimura, Junya
	Kitahira, Yukiko
	Takayama, Shun
	Kishimoto, Satoko
	Matsumiya-Matsumoto, Yuka
	Matsunaga, Kazuhide
	Imai, Tomoaki
	Uzawa, Narikazu
DC.publisher	Springer Science and Business Media B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-08-10
DC.identifier	https://doi.org/10.1007/s10585-024-10306-1
DC.subject	Epithelial-mesenchymal transition
	Inflammatory cytokine
	Oral cancer
	Syngeneic mouse oral cancer model
	Tumor microenvironment
DC.description	The version of record of this article, first published in Clinical and Experimental Metastasis, is available online at Publisher’s website: https://doi.org/10.1007/s10585-024-10306-1.
DCTERMS.abstract	The process of cervical lymph node metastasis is dependent on the phenotype of the tumor cells and their interaction with the host microenvironment and immune system; conventional research methods that focus exclusively on tumor cells are limited in their ability to elucidate the metastatic mechanism. In cancer tissues, a specialized environment called the tumor microenvironment (TME) is established around tumor cells, and inflammation in the TME has been reported to be closely associated with the development and progression of many types of cancer and with the response to anticancer therapy. In this study, to elucidate the mechanism of metastasis establishment, including the TME, in the cervical lymph node metastasis of oral cancer, we established a mouse-derived oral squamous cell carcinoma cervical lymph node highly metastatic cell line and generated a syngeneic orthotopic transplantation mouse model. In the established highly metastatic cells, epithelial-mesenchymal transition (EMT) induction was enhanced compared to that in parental cells. In the syngeneic mouse model, lymph node metastasis was observed more frequently in tumors of highly metastatic cells than in parental cells, and Cyclooxygenase-2 (COX-2) expression and lymphatic vessels in primary tumor tissues were increased, suggesting that this model is highly useful. Moreover, in the established highly metastatic cells, EMT induction was enhanced compared to that in the parent cell line, and CCL5 and IL-6 secreted during inflammation further enhanced EMT induction in cancer cells. This suggests the possibility of a synergistic effect between EMT induction and inflammation. This model, which allows for the use of two types of cells with different metastatic and tumor growth potentials, is very useful for oral cancer research involving the interaction between cancer cells and the TME in tumor tissues and for further searching for new therapeutic agents.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98110
citation_title	Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model
citation_author	Tobe-Nishimoto, Ayano
	Morita, Yoshihiro
	Nishimura, Junya
	Kitahira, Yukiko
	Takayama, Shun
	Kishimoto, Satoko
	Matsumiya-Matsumoto, Yuka
	Matsunaga, Kazuhide
	Imai, Tomoaki
	Uzawa, Narikazu
citation_publisher	Springer Science and Business Media B.V.
citation_language	English
citation_date	2024-08-10
citation_journal_title	Clinical and Experimental Metastasis
citation_volume	41
citation_issue	6
citation_firstpage	891
citation_lastpage	908
citation_doi	https://doi.org/10.1007/s10585-024-10306-1
citation_public_url	https://hdl.handle.net/11094/98110

Tumor microenvironment dynamics in oral cancer: unveiling the role of inflammatory cytokines in a syngeneic mouse model

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