Identification of tumour-reactive lymphatic endothelial cells capable of inducing progression of gastric cancer

鉴定能够诱导胃癌进展的肿瘤反应性淋巴管内皮细胞

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作者:Mao Watanabe Tokumoto, Hiroaki Tanaka, Yukie Tauchi, Hiroaki Kasashima, Kento Kurata, Masakazu Yashiro, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Ryosuke Amano, Kenjiro Kimura, Kazuya Muguruma, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa

Background

Tumour cells and stromal cells interact in the tumour microenvironment; moreover, stromal cells can acquire abnormalities that contribute to tumour progression. However, interactions between lymphatic endothelial cells (LECs) and tumour cells are largely unexamined. In this study, we aimed to determine whether tumour-specific LECs inhabit the tumour microenvironment and examine their influence on this microenvironment.

Conclusions

Our results demonstrated that LECs interacted with tumour cells and obtained abnormal phenotypes that could have important roles in tumour progression.

Methods

We isolated normal LECs (NLECs) from a non-metastatic lymph node and tumour-associated LECs (TLECs) from cancerous lymph nodes. We examined proliferative and migratory potency, growth factor production, and gene expression of each type of LEC. Moreover, we developed a co-culture system to investigate the interactions between gastric cancer cells and LECs.

Results

When compared with NLEC, TLECs had an abnormal shape, high proliferative and migratory abilities, and elevated expression of genes associated with inflammation, cell growth, and cell migration. NLECs co-cultured with gastric cancer cells from the OCUM12 cell line acquired TLEC-like phenotypes. Also, OCUM12 cells co-cultured with TLECs expressed high levels of genes responsible for metastasis. Conclusions: Our results demonstrated that LECs interacted with tumour cells and obtained abnormal phenotypes that could have important roles in tumour progression.

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