High expression of CCL2 in tumor cells and abundant infiltration with CD14 positive macrophages predict early relapse in breast cancer

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Heiskala , M , Leidenius , M , Joensuu , K & Heikkilä , P 2019 , ' High expression of CCL2 in tumor cells and abundant infiltration with CD14 positive macrophages predict early relapse in breast cancer ' , Virchows Archiv , vol. 474 , no. 1 , pp. 3-12 . https://doi.org/10.1007/s00428-018-2461-7

Title: High expression of CCL2 in tumor cells and abundant infiltration with CD14 positive macrophages predict early relapse in breast cancer
Author: Heiskala, Marja; Leidenius, Marjut; Joensuu, Kristiina; Heikkilä, Päivi
Contributor organization: II kirurgian klinikka
Department of Surgery
Clinicum
Department of Oncology
University of Helsinki
Department of Pathology
Medicum
HUSLAB
HUS Comprehensive Cancer Center
Date: 2019-01
Language: eng
Number of pages: 10
Belongs to series: Virchows Archiv
ISSN: 0945-6317
DOI: https://doi.org/10.1007/s00428-018-2461-7
URI: http://hdl.handle.net/10138/298729
Abstract: Macrophages are important for the function of the innate immune system, and in solid tumors, they represent a significant proportion of the tumor mass. Tumor-associated macrophages (TAM) have a M2 phenotype and show a multitude of pro-tumoral functions, promoting tumor cell survival, proliferation, and dissemination. CCL2, synthesized by tumor and stromal cells, initiates a chemokine cascade inducing these processes. We studied by immunohistochemistry (IHC) the frequency of TAMs and CCL2 expressing cells in three groups of primary tumor (PT)-recurrence (R) pairs, where relapse was recorded within 2years (group 1), between 5 and 10years (group 2), and after 10years (group 3). In our study all established breast cancers were heavily infiltrated by CD68 positive cells. Both in PTs and in R lesions the infiltration was more abundant in the peritumoral than in the intratumoral stroma. The mean frequency of M2 marker and CD14 positive cells in the intratumoral stroma and CCL2 expressing tumor cells was higher in the Rs as compared to the corresponding PTs. In PTs, a high frequency of CD14 positive cells and a high expression of CCL2 by tumor cells was associated with an early recurrence. The findings support the current understanding of immune cell orchestrated development, progression and metastatic spread of breast cancer. Our study showed that a high frequency of CCL2 positive tumor cells and CD14 positive TAMs are significant risk factors for rapid tumor recurrence. Potential targets for intervention are discussed.
Subject: Innate immunity
Breast cancer
CCL2
CD14 positive macrophages
Prognostic markers in breast cancer
DISTINCT SUBSETS
ANGIOGENESIS
INHIBITION
MONOCYTES
3122 Cancers
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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