Depletion of cytosolic phospholipase A 2 in bone marrow-derived macrophages protects against lung cancer progression and metastasis

Mary C.M. Weiser-Evans, Xue Qing Wang, Jay Amin, Vicki Van Putten, Rashmi Choudhary, Robert A. Winn, Robert Scheinman, Peter Simpson, Mark W. Geraci, Raphael A. Nemenoff

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43 Scopus citations

Abstract

Cancer progression and metastasis involves interactions between tumor cells and the tumor microenvironment (TME). We reported that mice deficient for cytosolic phospholipase A2 (cPLA2-KO) are protected against the development of lung tumors. The goal of this study was to examine the role of CPLA2 in the TME. Mouse lung cancer cells (CMT167 and Lewis lung carcinoma cells) injected directly into lungs of syngeneic mice formed a primary tumor, and then metastasized to other lobes of the lung and to the mediastinal lymph nodes. Identical cells injected into CPLA2-KO mice showed a dramatic decrease in the numbers of secondary metastatic tumors. This was associated with decreased macrophage staining surrounding the tumor. Wild-type mice transplanted with CPLA2-KO bone marrow had a marked survival advantage after inoculation with tumor cells compared with mice receiving wild-type (WT) bone marrow. In vitro, coculturing CMT167 cells with bone marrow-derived macrophages from WT mice increased production of interleukin 6 (IL-6) by cancer cells. This increase was blocked in cocultures using CPLA2-KO macrophages. Correspondingly, IL-6 staining was decreased in tumors grown in CPLA2-KO mice. These data suggest that stromal CPLA2 plays a critical role in tumor progression by altering tumor-macrophage interactions and cytokine production,

Original languageEnglish (US)
Pages (from-to)1733-1738
Number of pages6
JournalCancer Research
Volume69
Issue number5
DOIs
StatePublished - Mar 1 2009

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Weiser-Evans, M. C. M., Wang, X. Q., Amin, J., Van Putten, V., Choudhary, R., Winn, R. A., Scheinman, R., Simpson, P., Geraci, M. W., & Nemenoff, R. A. (2009). Depletion of cytosolic phospholipase A 2 in bone marrow-derived macrophages protects against lung cancer progression and metastasis. Cancer Research, 69(5), 1733-1738. https://doi.org/10.1158/0008-5472.CAN-08-3766