炎性乳腺癌是导致乳腺癌女性患者死亡的最主要的癌症类型之一，炎性乳腺癌细胞能通过淋巴结转移及和血行转移至新的靶器官，进而形成转移灶导致病情的恶化。
早期研究证实细胞间一重要粘附分子--纤维连接蛋白的过表达会促进肿瘤发生转移，在正常胚胎形成过程中，纤维连接蛋白主要参与伤口愈合以及细胞的迁移。
单核细胞（白细胞中一种）分泌的免疫调节因子能提高炎性乳腺癌细胞中纤维连接蛋白的表达，促进乳腺癌病情的发展。近来，发表在Cell Communication and Signaling杂志上的一项研究证实：炎性乳腺癌细胞主要通过调控IL-8来提高纤维连接蛋白的表达，进而导致乳腺癌的恶化。白介素-8（IL-8）主要由单核细胞分泌的一种抗炎因子。
研究人员在该项研究中运用一系列细胞因子的抗体来鉴定炎性乳腺癌患者体内单核细胞能分泌出哪些免疫调节因子包括各类细胞因子、生长因子以及趋化因子等，结果发现单核细胞分泌的其他免疫调节因子的量均很少，但IL-8的分泌量却比正常单核细胞高出10倍以上。
工作人员总结道：炎性乳腺癌细胞中IL-8表达的提高，激活了PI3K-AK信号通路，进而能增加纤维连接蛋白的形成。(生物谷 Bioon.com)
doi:10.1186/1478-811X-10-3
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Monocytes conditioned media stimulate fibronectin expression and spreading of inflammatory breast cancer cells in three-dimensional culture: A mechanism mediated by IL-8 signaling pathway
Mona M Mohamed
Background
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer characterized by invasion of carcinoma cells into dermal lymphatic vessels where they form tumor emboli over expressing adhesion molecule E-cadherin. Although invasion and metastasis are dynamic processes controlled by complex interaction between tumor cells and microenvironment the mechanisms by which soluble mediators may regulate motility and invasion of IBC cells are poorly understood. The present study investigated the effect of media conditioned by human monocytes U937 secreted cytokines, chemokines and growth factors on the expression of adhesion molecules E-cadherin and fibronectin of human IBC cell line SUM149. Furthermore, cytokines signaling pathway involved in were also identified.
Results
U937 secreted cytokines, chemokines and growth factors were characterized by cytokine antibody array. The major U937 secreted cytokines/chemokines were interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1/CCL2). When SUM149 cells were seeded in three dimensional (3D) models with media conditioned by U937 secreted cytokines, chemokines and growth factors; results showed: 1) changes in the morphology of IBC cells from epithelial to migratory spindle shape branched like structures; 2) Over-expression of adhesion molecule fibronectin and not E-cadherin. Further analysis revealed that over-expression of fibronectin may be mediated by IL-8 via PI3K/Akt signaling pathway.
Conclusion
The present results suggested that cytokines secreted by human monocytes may promote chemotactic migration and spreading of IBC cell lines. Results also indicated that IL-8 the major secreted cytokine by U937 cells may play essential role in fibronectin expression by SUM149 cells via interaction with IL-8 specific receptors and stimulation of PI3K/Akt signaling pathway.
