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

Eur J Immunol. 1998 Aug;28(8):2530-6. doi: 10.1002/(SICI)1521-4141(199808)28:08<2530::AID-IMMU2530>3.0.CO;2-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / chemistry
  • Antigens, CD / physiology*
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / pathology
  • Cell Movement / immunology
  • Chemokine CCL2 / biosynthesis
  • Endothelium / immunology
  • Endothelium / pathology
  • Extracellular Matrix / immunology
  • Humans
  • In Vitro Techniques
  • Integrin alpha1
  • Interleukin-8 / biosynthesis
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology

Substances

  • Antigens, CD
  • Chemokine CCL2
  • Integrin alpha1
  • Interleukin-8