The role of some cytokines as a local microenvironment in breast cancer progression

Semesiuk N., Bezdenezhnykh N., Lykhova A., Kudryavets Yu.I.

N. Semesiuk, N. Bezdenezhnykh, A. Lykhova, Yu. Kudryavets

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine,

IntroductionBreast cancer (BC) is a leading cause of cancer death among women. In most cases, death results from the dissemination of cancer cells and the development of distant metastases. Approximately 65–75% of patients with advanced breast cancer will develop bone metastases, which result in bone destruction. The presence of disseminated tumor cells (DTC) in bone marrow (BM) of BC patients has been proven to have clinical relevance. Despite the clinical significance of DTCs in the BM, the biological relevance remains controversial. Microenvironment plays an important role in tumor progression both within primary tumor and distant metastases in secondary sites. BM is a depot of various growth factors. It is not excluded that increased level of some cytokines may serve as the additional factor of prediction progression of tumor growth, because certain cytokines create the microenvironmental conditions for the establishment of distant metastases from a primary BC. Therefore, a search of new comprehensive prognostic algorithm, based on simultaneous detection of DTC in BM and cytokine profile in BC patients, should promote the development of personalized therapeutic approaches. Aim: The aim of this study was to detect DTC in BM and determine an impact of cytokine status of peripheral blood (PB) and BM of primary BC patients to cancer prognosis. Methods: Immunocytochemistry, bioassay tests, ELISA, cultivation tests and statistical methods. ResultsIn our study DTC in samples of BM was revealed in 50% breast cancer patients of progression group. The level of TNF, CSF-1, IL-6, TGF-β1, VEGF and IFN was analysed. It was found that most significant additional markers of tumor progression with detection of DTC in BM are the levels of TNF in BM and PB, of CSF-1 and IL-6 in PB and of endogenous IFN in BM and PB of BC patients. In patients of disease progression group in comparison with patients in remission group the levels of TNF in BM were increased by 44% (< 0.01), of CSF-1 and IL-6 in PB — by more than on 40–60% (< 0.05). Conclusion: Comprehensive detection of DTC in BM and identification of the levels of TNF, IFN, CSF-1, VEGF, IL-6 and TGF- β1 in PB and BM of BC patients could be one of the ways to predict metastatic process and correct antitumor individualized therapy.

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