炎性乳腺癌是導(dǎo)致乳腺癌女性患者死亡的最主要的癌癥類型之一，炎性乳腺癌細(xì)胞能通過淋巴結(jié)轉(zhuǎn)移及和血行轉(zhuǎn)移至新的靶器官,，進而形成轉(zhuǎn)移灶導(dǎo)致病情的惡化。
早期研究證實細(xì)胞間一重要粘附分子--纖維連接蛋白的過表達會促進腫瘤發(fā)生轉(zhuǎn)移,，在正常胚胎形成過程中,，纖維連接蛋白主要參與傷口愈合以及細(xì)胞的遷移。
單核細(xì)胞（白細(xì)胞中一種）分泌的免疫調(diào)節(jié)因子能提高炎性乳腺癌細(xì)胞中纖維連接蛋白的表達,，促進乳腺癌病情的發(fā)展,。近來，發(fā)表在Cell Communication and Signaling雜志上的一項研究證實：炎性乳腺癌細(xì)胞主要通過調(diào)控IL-8來提高纖維連接蛋白的表達,，進而導(dǎo)致乳腺癌的惡化,。白介素-8（IL-8）主要由單核細(xì)胞分泌的一種抗炎因子。
研究人員在該項研究中運用一系列細(xì)胞因子的抗體來鑒定炎性乳腺癌患者體內(nèi)單核細(xì)胞能分泌出哪些免疫調(diào)節(jié)因子包括各類細(xì)胞因子,、生長因子以及趨化因子等,，結(jié)果發(fā)現(xiàn)單核細(xì)胞分泌的其他免疫調(diào)節(jié)因子的量均很少，但IL-8的分泌量卻比正常單核細(xì)胞高出10倍以上,。
工作人員總結(jié)道：炎性乳腺癌細(xì)胞中IL-8表達的提高,，激活了PI3K-AK信號通路，進而能增加纖維連接蛋白的形成,。(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.
