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能够诱导胃癌进展的肿瘤反应性淋巴管内皮细胞的鉴定。

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

作者信息

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

机构信息

Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

出版信息

Br J Cancer. 2015 Sep 29;113(7):1046-54. doi: 10.1038/bjc.2015.282. Epub 2015 Sep 10.

DOI:10.1038/bjc.2015.282
PMID:26355233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4651131/
Abstract

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.

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.

摘要

背景

肿瘤细胞与基质细胞在肿瘤微环境中相互作用；此外，基质细胞可出现促进肿瘤进展的异常变化。然而，淋巴管内皮细胞（LECs）与肿瘤细胞之间的相互作用在很大程度上尚未得到研究。在本研究中，我们旨在确定肿瘤特异性淋巴管内皮细胞是否存在于肿瘤微环境中，并研究它们对该微环境的影响。

方法

我们从非转移性淋巴结中分离出正常淋巴管内皮细胞（NLECs），并从癌性淋巴结中分离出肿瘤相关淋巴管内皮细胞（TLECs）。我们检测了每种类型淋巴管内皮细胞的增殖和迁移能力、生长因子产生情况以及基因表达。此外，我们建立了共培养系统来研究胃癌细胞与淋巴管内皮细胞之间的相互作用。

结果

与NLEC相比，TLECs形态异常，具有较高的增殖和迁移能力，且与炎症、细胞生长和细胞迁移相关的基因表达升高。与来自OCUM12细胞系的胃癌细胞共培养的NLECs获得了TLEC样表型。此外，与TLECs共培养的OCUM12细胞表达了高水平的与转移相关的基因。

结论

我们的结果表明，淋巴管内皮细胞与肿瘤细胞相互作用并获得异常表型，这些表型可能在肿瘤进展中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/699236129d1c/bjc2015282f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/be9b73523161/bjc2015282f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/934fa0352fff/bjc2015282f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/e15a661b2aef/bjc2015282f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/cb73064dd06a/bjc2015282f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/4139985af97f/bjc2015282f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/699236129d1c/bjc2015282f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/be9b73523161/bjc2015282f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/934fa0352fff/bjc2015282f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/e15a661b2aef/bjc2015282f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/cb73064dd06a/bjc2015282f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/4139985af97f/bjc2015282f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/4651131/699236129d1c/bjc2015282f6.jpg

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