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

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.

journal_name

Eur J Immunol

authors

Ferrero E,Fabbri M,Poggi A,Galati G,Bernasconi S,Zocchi MR

doi

10.1002/(SICI)1521-4141(199808)28:08<2530::AID-IMM

subject

Has Abstract

pub_date

1998-08-01 00:00:00

pages

2530-6

issue

8

eissn

0014-2980

issn

1521-4141

pii

10.1002/(SICI)1521-4141(199808)28:08<2530::AID-IMM

journal_volume

28

pub_type

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