TY - JOUR
T1 - Tumor-driven matrix invasion by infiltrating lymphocytes
T2 - Involvement of the α1 integrin I-domain
AU - Ferrero, Elisabetta
AU - Fabbri, Monica
AU - Poggi, Alessandro
AU - Galati, Giacomo
AU - Bernasconi, Sergio
AU - Zocchi, Maria Raffaella
PY - 1998/8
Y1 - 1998/8
N2 - 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 (MOP-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 MOP-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 α1 integrin, which acts through its I-domain that is up-regulated 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 α1 integrin-mediated pathway of matrix invasion.
AB - 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 (MOP-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 MOP-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 α1 integrin, which acts through its I-domain that is up-regulated 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 α1 integrin-mediated pathway of matrix invasion.
KW - Adhesion molecule
KW - Chemokine
KW - Extracellular matrix
KW - Integrin
KW - Tumor-infiltrating lymphocyte
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U2 - 10.1002/(SICI)1521-4141(199808)28:08<2530::AID-IMMU2530>3.0.CO;2-6
DO - 10.1002/(SICI)1521-4141(199808)28:08<2530::AID-IMMU2530>3.0.CO;2-6
M3 - Article
C2 - 9710230
AN - SCOPUS:0031926716
VL - 28
SP - 2530
EP - 2536
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 8
ER -