Dendritic cells (DCs) are immune cells that surveil the organism for infections or malignancies and activate specific T lymphocytes initiating specific immune responses. Contrariwise, DCs have been show to participate in the development of diseases, among them some types of cancer by inducing angiogenesis or immunosuppression. The ultimate fate of DC functions regarding their role in disease or health is prompted by signals from the microenvironment. We have previously shown that the interaction of DCs with various extracellular matrix components modifies the immune properties and angiogenic potential of these cells. The objective of the current studies was to investigate the angiogenic and immune profile of murine myeloid DCs upon interaction with laminin environments, with a particular emphasis on ovarian cancer. Our results show that murine ovarian tumors produce several types of laminins, as determined by PCR analysis, and also that tumor-associated DCs, both from ascites or solid tumors express adhesion molecules capable of interacting with these molecules as determined by flow cytometry and PCR analysis. Further, we established that DCs cultured on laminin upregulate both AKT and MEK signaling pathways, and that long-term culture on laminin surfaces decreases the immunological capacities of these cells when compared to the same cells cultured on synthetic substrates. In addition, we observed that tumor conditioned media was able to modify the metabolic status of these cells, and also reprogram the development of DCs from bone marrow precursors towards the generation of myeloid-derived suppressor cells. Overall, these studies demonstrate that the interaction between soluble factors and extracellular matrix components of the ovarian cancer microenvironment shape the biology of DCs and thus help them become co-conspirators of tumor growth.

中文翻译：

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层粘连蛋白环境和肿瘤因素对髓样树突状细胞生物学的影响。

树突状细胞（DC）是一种免疫细胞，可以监视生物体是否发生感染或恶性肿瘤，并激活特定的T淋巴细胞以启动特定的免疫反应。相反，已证明DC参与疾病的发展，其中包括通过诱导血管生成或免疫抑制而引起的某些类型的癌症。DC功能在疾病或健康中的作用最终取决于其微环境的信号。先前我们已经表明DC与各种细胞外基质成分的相互作用修饰了这些细胞的免疫特性和血管生成潜能。当前研究的目的是研究与层粘连蛋白环境相互作用时鼠类髓系DC的血管生成和免疫特性，特别是卵巢癌。我们的结果表明，通过PCR分析确定，鼠卵巢肿瘤会产生几种类型的层粘连蛋白，而且通过腹水或实体瘤的流式细胞术和PCR分析，与腹水或实体瘤相关的DC均表达能够与这些分子相互作用的粘附分子。 。此外，我们建立了层粘连蛋白上培养的DC上调AKT和MEK信号通路，并且与在合成底物上培养的相同细胞相比，在层粘连蛋白表面上的长期培养降低了这些细胞的免疫能力。另外，我们观察到肿瘤条件培养基能够改变这些细胞的代谢状态，并且还重新编程了从骨髓前体向髓样来源的抑制性细胞生成DC的过程。总体，