Tumor-driven matrix invasion by infiltrating lymphocytes: involvement of the alpha1 integrin I-domain.

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.
AuthorsE Ferrero, M Fabbri, A Poggi, G Galati, S Bernasconi, M R Zocchi
JournalEuropean journal of immunology (Eur J Immunol) Vol. 28 Issue 8 Pg. 2530-6 (Aug 1998) ISSN: 0014-2980 [Print] GERMANY
PMID9710230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Chemokine CCL2
  • Integrin alpha1
  • Interleukin-8
  • 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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