Tumor-derived intercellular adhesion molecule-1 mediates tumor-associated leukocyte infiltration in orthotopic pancreatic xenografts

Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, the University of Texas Southwestern Medical School, Dallas, TX, USA.
Experimental Biology and Medicine (Impact Factor: 2.17). 02/2010; 235(2):263-70. DOI: 10.1258/ebm.2009.009215
Source: PubMed


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.

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    • "Previous murine studies have shown that the introduction of the ICAM-1 gene into tumor cells using retroviral vectors led to enhanced antitumor responses [5]. Furthermore, numerous studies have documented a link between the immune infiltrate and response to therapy [26,27]. Vesalainen et al. found that low numbers of tumor-infiltrating lymphocytes were a sign of high risk of tumor progression and fatal disease in an analysis with 325 cases with long-term follow-up [28]. "
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    Molecular Cancer 04/2014; 13(1):84. DOI:10.1186/1476-4598-13-84 · 4.26 Impact Factor
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    • "ICAM1 has a role in cell–cell and cell–extracellular matrix adhesion. ICAM1 has previously been reported to be overexpressed in pancreatic cancer, and serves as an important docking point for polymorphonuclear cells that functionally promote tumor cell metastasis [95,96]. BCAM is a laminin receptor and a member of the immunoglobulin superfamily. "
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    • "Ligands of LFA-1 include intercellular adhesion molecules (ICAMs; ICAM-1, -2, -3, -4, and -5) [5] and junctional adhesion molecule (JAM)-1 [6], both of which are the members of the immunoglobulin superfamily (IgSF) receptors. As one of the most biologically important ligands for LFA-1, ICAM-1 is expressed at a low constitutive level in diverse types of cells and tissues, while its expression is greatly upregulated in response to inflammation [7] and in some tumors and their stroma [8], [9], [10], [11], [12], [13], [14]. The interaction of LFA-1 and ICAM-1 is contained within the single domains called the α I domain in LFA-1 and the first N-terminal domain (D1) of ICAM-1. "
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