TY  - GEN
TY  - GEN
T1  - Stromal cells of mesenchymal origin in breast cancer
T2  - Acta Universitatis Ouluensis
A1  - Pasanen, Ilkka, 1987- kirjoittaja
LA  - eng
PP  - Oulu
PB  - University of Oulu
YR  - 2017
UL  - https://kansalliskirjasto.finna.fi/Record/fikka.4274438
AB  - Breast cancer, the most common cancer in women in Finland; its prognosis varies from very good to poor. During the last two decades, mesenchymal stromal cells, carcinoma-associated fibroblasts and normal fibroblasts of the breast have been investigated in the context of breast carcinomas because of their presence in the tumor microenvironment. It has been shown that the properties of the non-malignant tumor compartment possess prognostic value. The effects that these three stromal cell types have on cancer progression have been studied, but their exact mechanisms remain still largely unknown. This experimental work was conducted in order to investigate whether the three cell types of mesenchymal origin influence breast cancer cell proliferation in vitro and tumor growth in vivo. Functional and structural differences between the stromal cell types were investigated using multiple methods. A total of 19 primary human bone marrow derived mesenchymal stromal cell lines, and six paired primary fibroblast and carcinoma-associated fibroblast lines of the breast were used in the study. Co-cultures of labeled stromal cells and breast cancer cell lines MDA-MB-231, M-4A4 and NM-2C5 were performed and the proliferation properties of each cell line were assessed. An orthotopic murine breast cancer model was established by injecting NM-2C5 cancer cells in the mammary fat pads of athymic mice either alone or with the three stromal cell types, and tumor growth and histology were analysed. Mesenchymal stromal cells increased the proliferation of breast cancer cell lines NM-2C5 and MDA-MB-231, and carcinoma-associated fibroblasts increased the proliferation of NM-2C5 cells in vitro. The effect was due to both soluble factors and direct cell-cell contact. In the in vivo experiments, the mesenchymal stromal cells inhibited and the fibroblasts enhanced the growth of breast cancer tumors. Histological analysis of the tumors revealed differences in the invasiveness, necrosis and amount of connective tissue. Differences in the expression of CD105 and CD54 were observed between tumors with mesenchymal stromal cells or fibroblasts. Carcinoma-associated fibroblasts differed from mesenchymal stromal cells in their expressions of CD105 and CD54. The fibroblast subtypes differed at the gene expression level in immunological, developmental and extracellular matrix related pathways.
AB  - Alkuperältään mesenkymaaliset strooman solut rintasyövässä.
NO  - Artikkeliväitöskirjan yhteenveto-osa ja 3 eripainosta.
SN  - 978-952-62-1557-0 nidottu
KW  - rintasyöpä
KW  - syöpäsolut
KW  - sidekudokset
ER  -