Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8524945 | Biomedicine & Pharmacotherapy | 2018 | 8 Pages |
Abstract
Disparate roles exist for tumor-associated macrophages in breast cancer growth and progression. The aim of this study was to explore the influence of induced macrophages on the growth of breast cancer cells. THP-1 monocytes were differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect of the medium from THP-1 monocytes or macrophage-conditioned medium (MÏCM) on MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB; triple-negative) breast cancer cells was determined at 24â¯h, 48â¯h and 72â¯h. Assays were conducted for cell viability, apoptosis, proliferation and cell phenotype, and quantitative real-time polymerase chain reaction (qRT-PCR) for expression of associated genes. MÏCM inhibited proliferation of MCF-7 and MB cells in a time-dependent manner and, in particular, decreased viability of MCF-7 cells. MÏCM induced a markedly vacuolated phenotype in MCF-7 increased apoptosis in MCF-7 cells, but correlative changes in Bcl-2 or Bax were absent. A multifold and significant reduction in anti-apoptotic Bcl-2 in MB cells was not matched by increased apoptosis. The cell cycle inhibitor CDKN1A was increased in both cell lines, but PCNA decreased only in MB cells. Senescence-associated galactosidase beta-1 (GLB1) mRNA was decreased in MCF-7 cells (48 and 72â¯h) but increased in MB cells (72â¯h). Increased expression of interleukin-6 (IL-6) and IL-8 was seen in both cell lines, and increased tumor necrosis factor- α was seen at 24â¯h for MB and 72â¯h for MCF-7 indicating increased inflammatory responses of the cancer cells. The two breast cancer celllines had different responses to MÏCM, mainly involving inhibition rather than stimulation of growth of the cells, stimulation of senescence (MB cells) and increased inflammatory cytokine expression. The estrogen and progesterone receptor status of the cell lines may determine their response to MÏCM. The function of the inflammatory cytokines in breast cancer growth remains to be identified.
Keywords
PCNAGLB1CDKN1Aphorbol 12-myristate 13-acetateIL-6IL-8Bcl-2qRT-PCRDMSOPMAMTTProliferating Cell Nuclear AntigenAutophagyinflammationinterleukin 6Interleukin 8TAMTumor associated macrophagetumor necrosis factor- alphaApoptosisDimethyl sulfoxideBreast cancerTNF-αB-cell lymphoma-2Macrophagecyclin-dependent kinase inhibitor 1Aquantitative real-time polymerase chain reactionSenescence
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Authors
Wenzhe Song, Parth Thakor, David A. Vesey, Glenda C. Gobe, Christudas Morais,