Abstract
Breast cancer provides a typical example of an inflammation-linked malignant disease. The inflammatory components present in the tumor microenvironment contribute to the further progression of the disease. The present study was conducted to evaluate the correlation between levels of proinflammation cytokines tumor necrosis factor α, interleukin 1β, interleukin 6, C-reactive protein and tumor recurrence in breast cancer patients. Seventy two breast cancer patients with histologically proven diagnosis and 15 healthy donors were enrolled into study. Thirty one patients with progression of the disease and 41 patients with clinical stabilization (conditional remission) were included to “progression” and “remission” groups respectively. This division of breast cancer patients was made during the 3 years study. The levels of proinflammation cytokines – tumor necrosis factor α, interleukin 1β, interleukin 6 and C-reactive protein were revealed. This cytokines in bone marrow and peripheral blood act as a specific microenvironment and was found that the elevated levels of this cytokines were strongly associated with progression of breast cancer. The data showed that most prominent predictive markers of tumor recurrence are high levels of indicated cytokines in combination with other markers (C-reactive protein; disseminated tumor cells in bone marrow). Determination of the high levels of tumor necrosis factor, interleukin 1β, interleukin 6 in bone marrow and peripheral blood of breast cancer patients are important to establish the features of bone marrow microenvironment for prediction of metastasis and correction antitumor therapy. Keywords: breast cancer, proinflammatory cytokines, bone marrow, peripheral blood, disseminated tumor cells.
Highlights
Inflammatory pathways have garnered considerable interest as an important mediator of the molecular mechanisms leading to carcinogenesis
It is known that the development of cancers from inflammation might be a process driven by inflammatory cells and variety of mediators such as cytokines and chemokines which altogether form the part of tumor microenvironment [15]
Key features of cancer-related inflammation include the infiltration of leukocytes, prominently tumor-associated macrophages; the presence mediators of inflammation: cytokines, and chemokines (CCL2 and CXCL8) and the occurrence of tissue remodeling and angiogenesis [3]
Summary
Inflammatory pathways have garnered considerable interest as an important mediator of the molecular mechanisms leading to carcinogenesis. It is known that the development of cancers from inflammation might be a process driven by inflammatory cells and variety of mediators such as cytokines and chemokines which altogether form the part of tumor microenvironment [15]. Key features of cancer-related inflammation include the infiltration of leukocytes, prominently tumor-associated macrophages; the presence mediators of inflammation: cytokines (tumor necrosis factor, interleukin 1 and interleukin 6), and chemokines (CCL2 and CXCL8) and the occurrence of tissue remodeling and angiogenesis [3]. The tumor-promoting activities of tumor-associated macrophages may be the result of their ability to express numerous tumor-promoting characteristics, such as growth factors for breast tumor cells, angiogenic mediators, extracellular matrix degra ding enzymes and inflammatory cytokines [2]. Cytokine signaling could contri bute to the progression of tumors in two aspects: the stimulation of cell growth and differentiation and the inhibition of apoptosis of altered cells at the inflammatory site [5, 14]
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