STAT3 activation in endothelial cells is important for tumor metastasis via increased cell adhesion molecule expression
Abstract
Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis. We found that the loss of STAT3 in ECs did not affect primary Lewis lung carcinoma (LLC) tumor growth, but it reduced in vivo LLC metastasis in experimental and spontaneous metastasis models. Mechanistically, STAT3 activation upregulated cell adhesion molecule expression, including E-selectin and P-selectin, in murine endothelial MS-1 cells treated with tumor cell-conditioned media in vitro and in pre-metastatic lungs of tumor-bearing mice in vivo. We also found that both E-selectin and P-selectin were, at least in part, responsible for STAT3-induced adhesion and invasion of LLC cells through an EC monolayer. However, tumor cell-conditioned media from B16F10 melanoma cells did not activate STAT3 in MS-1 cells. As a result, EC STAT3 knockout did not affect B16F10 melanoma cell metastasis. In addition, various human cancer cells activated STAT3 in human ECs (HUVECs), resulting in increased cell adhesi…
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The JAK-STAT pathway regulates metastasis and tumor angiogenesis.
“The JAK-STAT pathway is known to regulate metastasis and tumor angiogenesis35–37”
From Endothelial Pim3 kinase protects the vascular barrier during lung metastasis (2024) · cites this paper as [35]
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- Authors
- Kim, K.-J., Kwon, S.-H., Yun, J.-H., Jeong, H.-S., Kim, H.-R., Lee, E. H., Ye, S.-K., & Cho, C.-H.
- Affiliations
- Seoul National University (KR)
- Catholic University of Korea (KR)
- Corresponding author
- Ye, S-K
- Cho, C-H
- ORCID
- Lee, E H
- Venue
- Oncogene
- Published
- 2017-05-22
- Volume
- 36
- Issue
- 39
- Pages
- 5445-5459
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2620162514
- Cited by
- 70
- References
- 51
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 4 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 10
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- STAT3, endothelial cells, metastasis, adhesion molecules, E-selectin, P-selectin, Lewis lung carcinoma, melanoma, tumor cell adhesion, tumor invasion
- MeSH terms
- A549 Cells, Animals, Cell Communication, Humans, Melanoma, Experimental, Mice, Inbred C57BL, Neoplasm Metastasis, Neoplasms, Cell Adhesion Molecules, Mice, Knockout, Endothelial Cells, HCT116 Cells, Cell Line, Tumor, STAT3 Transcription Factor, Mice
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