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Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma

The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral ca...

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Autores principales: Ohata, Yae, Tsuchiya, Maiko, Hirai, Hideaki, Yamaguchi, Satoshi, Akashi, Takumi, Sakamoto, Kei, Yamaguchi, Akira, Ikeda, Tohru, Kayamori, Kou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812599/
https://www.ncbi.nlm.nih.gov/pubmed/29444110
http://dx.doi.org/10.1371/journal.pone.0191865
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author Ohata, Yae
Tsuchiya, Maiko
Hirai, Hideaki
Yamaguchi, Satoshi
Akashi, Takumi
Sakamoto, Kei
Yamaguchi, Akira
Ikeda, Tohru
Kayamori, Kou
author_facet Ohata, Yae
Tsuchiya, Maiko
Hirai, Hideaki
Yamaguchi, Satoshi
Akashi, Takumi
Sakamoto, Kei
Yamaguchi, Akira
Ikeda, Tohru
Kayamori, Kou
author_sort Ohata, Yae
collection PubMed
description The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral cancer cells and fibroblasts, which are major cellular components of the tumor stroma, we conducted an in vitro study by using human oral squamous cell carcinoma (OSCC) cell lines and normal human dermal fibroblasts (NHDFs). The results of transwell assays revealed that the migration and invasion of 2 OSCC cell lines, HO1-N-1 and HSC3, were markedly stimulated upon coculturing with NHDFs. To investigate the factors that promote tumor invasion, we isolated NHDFs from cocultures prepared with HO1-N-1 cells and performed microarray analysis. Among the various genes that were upregulated, we identified the gene encoding leukemia inhibitory factor (LIF), and we focused on LIF in further analyses. We confirmed that all OSCC-derived conditioned media potently upregulated LIF expression in NHDFs, and the results of our transwell analysis demonstrated that NHDF-induced OSCC migration and invasion were inhibited by LIF-neutralizing antibodies. Furthermore, immunohistochemical analysis of patient samples revealed that in 44 out of 112 OSCC cases, LIF was expressed in the tumor stroma, particularly in cancer-associated fibroblasts (CAFs), and, notably, clinicopathological analyses confirmed that LIF expression in CAFs was significantly correlated with increased depth of tumor invasion. Collectively, our results suggest that OSCC stimulates fibroblasts to produce LIF, which, in turn, participates in cancer-cell invasion. Our finding offers a potential therapeutic strategy targeting the cancer stroma for the treatment of OSCC patients.
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spelling pubmed-58125992018-02-28 Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma Ohata, Yae Tsuchiya, Maiko Hirai, Hideaki Yamaguchi, Satoshi Akashi, Takumi Sakamoto, Kei Yamaguchi, Akira Ikeda, Tohru Kayamori, Kou PLoS One Research Article The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral cancer cells and fibroblasts, which are major cellular components of the tumor stroma, we conducted an in vitro study by using human oral squamous cell carcinoma (OSCC) cell lines and normal human dermal fibroblasts (NHDFs). The results of transwell assays revealed that the migration and invasion of 2 OSCC cell lines, HO1-N-1 and HSC3, were markedly stimulated upon coculturing with NHDFs. To investigate the factors that promote tumor invasion, we isolated NHDFs from cocultures prepared with HO1-N-1 cells and performed microarray analysis. Among the various genes that were upregulated, we identified the gene encoding leukemia inhibitory factor (LIF), and we focused on LIF in further analyses. We confirmed that all OSCC-derived conditioned media potently upregulated LIF expression in NHDFs, and the results of our transwell analysis demonstrated that NHDF-induced OSCC migration and invasion were inhibited by LIF-neutralizing antibodies. Furthermore, immunohistochemical analysis of patient samples revealed that in 44 out of 112 OSCC cases, LIF was expressed in the tumor stroma, particularly in cancer-associated fibroblasts (CAFs), and, notably, clinicopathological analyses confirmed that LIF expression in CAFs was significantly correlated with increased depth of tumor invasion. Collectively, our results suggest that OSCC stimulates fibroblasts to produce LIF, which, in turn, participates in cancer-cell invasion. Our finding offers a potential therapeutic strategy targeting the cancer stroma for the treatment of OSCC patients. Public Library of Science 2018-02-14 /pmc/articles/PMC5812599/ /pubmed/29444110 http://dx.doi.org/10.1371/journal.pone.0191865 Text en © 2018 Ohata et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ohata, Yae
Tsuchiya, Maiko
Hirai, Hideaki
Yamaguchi, Satoshi
Akashi, Takumi
Sakamoto, Kei
Yamaguchi, Akira
Ikeda, Tohru
Kayamori, Kou
Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
title Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
title_full Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
title_fullStr Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
title_full_unstemmed Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
title_short Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
title_sort leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812599/
https://www.ncbi.nlm.nih.gov/pubmed/29444110
http://dx.doi.org/10.1371/journal.pone.0191865
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