Blot E, Chen W, Vasse M, Paysant J, Denoyelle C, Pillé J-Y, Vincent L, Vannier J-P, Soria J, Soria C
DIFEMA Laboratory, Medicine and Pharmacy Faculty, Cedex, France.
Br J Cancer. 2003 Apr 22;88(8):1207-12. doi: 10.1038/sj.bjc.6600872.
In breast cancers, clinical symptoms of inflammation localised around the tumour at the time of diagnosis have been considered to have poor prognosis significance. In this study, the biological mechanisms responsible for the deleterious action of monocytes in cancer were investigated. The incubation of the breast-cancer-derived MDA-MB231 cells with monocytes resulted in an increase in factors involved in cell invasion (i.e. both cancer cells and monocytes-associated urokinase and Tissue Factor, and PAI-1 and MMP-9 secretion). Moreover, the functions of monocytes were also modified. Incubation of monocytes with MDA-MB231 cancer cells resulted in a downregulation in the secretion of the antiproliferative cytokine Oncostatin M, while the apoptotic factor TNF alpha was dramatically increased. However, MDA-MB231 cancer cells have been shown to be resistant towards the apoptotic action of TNF alpha. These findings demonstrate that incubation of MDA-MB231 cancer cells with monocytes induced a crosstalk, which resulted in an increased expression of factors involved in cancer cell invasiveness and in a modification of monocytes function against cancer cells, while inflammatory effects were increased.
在乳腺癌中，诊断时肿瘤周围局部炎症的临床症状被认为具有不良预后意义。在本研究中，对单核细胞在癌症中有害作用的生物学机制进行了研究。将乳腺癌来源的MDA-MB231细胞与单核细胞共同培养，导致参与细胞侵袭的因子增加（即癌细胞和单核细胞相关的尿激酶、组织因子，以及PAI-1和MMP-9的分泌）。此外，单核细胞的功能也发生了改变。将单核细胞与MDA-MB231癌细胞共同培养导致抗增殖细胞因子制瘤素M的分泌下调，而凋亡因子肿瘤坏死因子α则显著增加。然而，MDA-MB231癌细胞已被证明对肿瘤坏死因子α的凋亡作用具有抗性。这些发现表明，MDA-MB231癌细胞与单核细胞共同培养诱导了一种相互作用，这导致参与癌细胞侵袭的因子表达增加，单核细胞对癌细胞的功能发生改变，同时炎症效应增强。
