Tumor-derived intercellular adhesion molecule-1 mediates tumor-associated leukocyte infiltration in orthotopic pancreatic xenografts.
Tumor infiltration of immune cells (polymorphonuclear cells [PMNs] and macrophages) was initially thought to be an attempt by the host organism to combat malignancy. It appears, however, that certain subsets of chronically activated immune cells likely promote tumor growth, facilitate tumor cell survival and aid in metastasis. The association between tumor cells and tumor-associated PMNs has been demonstrated in several types of cancer, but the presence of tumor-associated PMNs in pancreatic cancer has not been well studied in vivo. Intercellular adhesion molecule-1 (ICAM-1) functions in cell-cell and cell-extracellular matrix adhesion and has a physiological role in PMN tight adhesion of leukocytes via interaction with the ligands LFA-1 and Mac-1. Increased ICAM-1 expression correlates with poor prognosis in pancreatic cancer. Therefore, the aim of this study was to investigate the function of ICAM-1 and tumor-associated PMNs in pancreatic cancer progression using ICAM-1-null (ICAM-1(-/-)) mice. We hypothesize that ICAM-1 null mice have decreased pancreatic cancer progression. Surprisingly, there is no significant difference in pancreatic cancer progression in wild-type versus ICAM-1 null mice. Interestingly, we found that tumor-derived ICAM-1 co-localizes with host PMNs at the leading edge of the tumor in ICAM-1 null mice. These results suggest that tumor-derived ICAM-1 is a sufficient ligand for tumor-associated PMNs and may play a role in subsequent tumor growth and metastasis.
Roland
Christina L
CL
Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, the University of Texas Southwestern Medical School, Dallas, TX, USA.
Dineen
Sean P
SP
Toombs
Jason E
JE
Carbon
Juliet G
JG
Smith
C Wayne
CW
Brekken
Rolf A
RA
Barnett
Carlton C
CC
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
D017931:DNA Primers; C090509:Icam1 protein, mouse; D018799:Intercellular Adhesion Molecule-1