Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines |
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Authors: | Douglas A Arenberg Michael P Keane Bruno DiGiovine Steven L Kunkel Scott R B Strom Marie D Burdick Mark D Iannettoni Robert M Strieter |
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Institution: | (1) University of Michigan Medical Center, Division of Pulmonary and Critical Care, 6301 MSRB III, Box 0642, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA Tel.: +1-734-936-2612 Fax: +1-734-764-4556 e-mail: darenber@umich.edu, US;(2) Henry Ford Hospital, Division of Pulmonary Medicine, Detroit, Mich., USA, US;(3) University of Michigan Medical Center, Department of Pathology, Ann Arbor, Mich., USA, US;(4) University of Michigan Medical Center, Department of Surgery, Ann Arbor, Mich., USA, US;(5) Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Los Angeles (UCLA), Los Angeles, Calif., USA, US |
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Abstract: | Bronchogenic carcinoma is the leading cause of malignancy-related mortality in the United States, with an overall 5-year
survival rate of less than 15%. This aggressive behavior reflects, among other traits, the capacity of the tumor to evade
normal host immune defenses, and to induce a pro-angiogenic environment. A central feature of any immune response toward tumors
is the recruitment of specific immune cell populations. In the present study we investigated the infiltration of monocytes
in human specimens of non-small-cell lung cancer (NSCLC). The presence of macrophages in NSCLC tumors was documented by immunohistochemistry.
In vitro chemotaxis assays demonstrated higher monocyte chemotactic activity in NSCLC tumor homogenates than in normal lung
tissue. We next investigated the expression of CC chemokines within specimens of NSCLC tumors. Levels of the CC chemokines
were higher in NSCLC tumor tissue than in normal lung tissue. Immunolocalization showed that the cells associated with antigenic
CC chemokines were the malignant tumor cells, as well as occasional stromal cells. Maximal inhibition of monocyte chemotaxis
induced by NSCLC in vitro occurred in the presence of neutralizing antibodies to MCP-1 and MIP-1β. On follow-up of 15 patients
in whom we quantified macrophage infiltration, we found that those with recurrence of disease had higher levels of macrophage
infiltration in their initial tumors. However, the functional significance of CC-chemokine-mediated macrophage infiltration
into NSCLC remains to be determined.
Received: 12 November 1999 / Accepted: 10 December 1999 |
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Keywords: | Macrophage Chemokine Tumor |
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