The effect of monocyte/macrophage/alveolar macrophage axis effect on metastasi̇s and immune modulation in breast cancer subtypes

Breast cancer is one of the most common cancer type among women. Lung is still the most common site of metastasis for breast cancer, followed by bone, liver and brain metastasis. It has been suggested that cancer stem cell/cancer initiating cells are responsible for metastasis of cancer and the population and/or percentage of cancer stem cells found in the primary tumor are responsible for this metastasis. Although there are many studies about cancer stem cell and their immune modulation/evasion in the literature, the axis between monocyte/macrophage/tissue resident macrophages and cancer stem cells is unknown. In addition, a cell line is not available for future studies on lung tissue resident macrophages. Within the scope of the thesis, an alveolar macrophage-like cell line (Al-Maq/D6P30-DAISY5) was generated from a monocytic cell line, THP-1, by spontaneous selection. This cell line has been characterized by using the markers CD206, CD163, CD169, CD11b, CD11c, CD14, HLA-DR, CD16 and CD68. While performing the spontaneous selection of the alveolar macrophage-like cell line, the condition that most favors differentiation was selected by using different surface and extracellular matrix components. The alveolar macrophage-like cell line was co-cultured with breast cancer cell lines to investigate the change in CD44/CD24 surface expression levels. Among the breast cancer cell lines used, MDA-MB-468 and T47D cells contained "mixed type" cancer stem cell subclones and mostly supported the alveolar macrophage character of these cells. While BT474 cells increased CD14+ monocyte subsets, it was determined that they were the cell line that stimulates the CD169 expression at least. As a results, it was determined that cancer stem cell subtypes could support different monocyte/macrophage and tissue resident macrophage subsets. With these data, it is aimed to elucidate the mechanism by planning mechanistic and functional studies.