ArticleThe American journal of pathology2005
Characterization of the host proinflammatory response to tumor cells during the initial stages of liver metastasis.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 145 citations in OpenAlex.
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- Breast cancer liver metastasis: Pathogenesis and clinical implications.Frontiers in oncology · 2022Review
- The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis.Cancers · 2021Review
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- Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives.Cancers · 2021Review
- Surgery for Colorectal Cancer: A Trigger for Liver Metastases Development? New Insights into the Underlying Mechanisms.Biomedicines · 2021Review
- The Role of Tumor Necrosis Factor in Manipulating the Immunological Response of Tumor Microenvironment.Frontiers in immunology · 2021Review
- Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis.Frontiers in bioengineering and biotechnology · 2021Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The influx of metastatic tumor cells into the liver triggers a rapid proinflammatory cytokine cascade. To further analyze this host response, we used intrasplenic/portal inoculation of green fluorescent protein-marked human and murine carcinoma cells and a combination of immunohistochemistry and confocal microscopy. The metastatic murine lung carcinoma H-59 or human colorectal carcinoma CX-1 cells triggered tumor necrosis factor (TNF)-alpha production by Kupffer cells located in sinusoidal vessels around the invading tumor cells. H-59 cells rapidly elicited a fourfold increase in the number of TNF-alpha(+) Kupffer cells relative to basal levels within 2 hours and this response declined gradually after 6 hours. Increased cytokine production in these mice was confirmed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay performed on isolated Kupffer cells. CX-1 cells elicited a more gradual response that peaked at 10 to 16 hours, remained high up to 48 hours, and involved CX-1-Kupffer cell attachment. Furthermore, the rapidly induced production of TNF-alpha was followed by increased expression of the vascular adhesion receptors E-selectin P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 on sinusoidal endothelial cells. This proinflammatory response was tumor-specific and was not observed with nonmetastatic murine M-27 or human MIP-101 carcinoma cells. These results identify Kupffer cell-mediated TNF-alpha production as an early, tumor-selective host inflammatory response to liver-invading tumor cells that may influence the course of metastasis.
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