Abstract |
Here we show that tumor cells (TC) from renal cancers regulate the migratory properties of autologous tumor-infiltrating lymphocytes (TIL), enhancing their ability to invade the extracellular matrix. A similar effect is exerted by human recombinant macrophage chemotactic protein 1 (MCP-1) and IL-8, chemokines known to increase T lymphocyte migration both across vascular endothelium and subendothelial matrix. We found that TC freshly derived from renal cell carcinoma surgical specimens constitutively secrete both IL-8 and MCP-1 and that TIL express both specific receptors. TIL matrix invasion elicited by TC is inhibited by the addition of neutralizing antisera specific for IL-8 and MCP-1, demonstrating the direct relationship between chemokine release by TC and TIL invasion. Of note, TIL invasion of the extracellular matrix requires the alpha1 integrin, which acts through its I-domain that is upregulated upon culture with MCP-1 and IL-8. Collectively, these findings suggest that TC may actively recruit TIL via the release of chemotactic factors that enhance an alpha1 integrin-mediated pathway of matrix invasion.
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Authors | E Ferrero, M Fabbri, A Poggi, G Galati, S Bernasconi, M R Zocchi |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 28
Issue 8
Pg. 2530-6
(Aug 1998)
ISSN: 0014-2980 [Print] Germany |
PMID | 9710230
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- Chemokine CCL2
- Integrin alpha1
- Interleukin-8
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Topics |
- Antigens, CD
(chemistry, physiology)
- Carcinoma, Renal Cell
(immunology, pathology)
- Cell Movement
(immunology)
- Chemokine CCL2
(biosynthesis)
- Endothelium
(immunology, pathology)
- Extracellular Matrix
(immunology)
- Humans
- In Vitro Techniques
- Integrin alpha1
- Interleukin-8
(biosynthesis)
- Kidney Neoplasms
(immunology, pathology)
- Lymphocytes, Tumor-Infiltrating
(immunology, pathology)
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