Department of Histology, Angiogenesis Research Center; Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania.
Mol Med Rep. 2012 May;5(5):1175-80. doi: 10.3892/mmr.2012.796. Epub 2012 Feb 17.
Mesenchymal stem cells (MSCs) are able to acquire endothelial-like characteristics but their involvement in regulating MSC vasculogenesis is more complex. MSCs are able to express endothelial markers when cultured in endothelial growth medium (EGM), proving their differentiation into endothelial-like cells. The aim of our study was to evaluate the capacity of the MCF-7 breast cancer cell line to stimulate the organization of regular MSCs and MSCs culture-expanded in EGM (MSCEs) into capillary-like structures and to assess the involvement of tumor-derived VEGF. We seeded MSCs and MSCEs on Matrigel in a Transwell two compartment culture system in the presence of VEGF, MCF-7 cells or their conditioned medium (CM). Both MSCs and MSCEs were CD31-negative, either in culture conditions, or in the Transwell system. MSCs had a clear tendency to organize in clusters and to form capillary-like structures, in the presence of VEGF or MCF-7 cells. MSCEs had a similar behavior, but their tendency to organize in clusters was lower. Neither MSCs nor MSCEs organized into capillary-like structures in the presence of MCF-7 CM, yet the tendency to organize in clusters was stronger in the MSCs. Following exposure both to EGM-2 alone and to EGM-2 supplemented with MSCs or MSCEs, the MCF-7 cells were present as adherent cells on the bottom of the lower wells, while the tendency to organize as single cells (and not in clusters) was more evident when MCF-7 cells were co-cultured with MSCs compared to the other conditions. Both breast cancer cells and VEGF stimulate MSCs and MSCEs to form capillary-like structures, indicating a role of tumor-derived VEGF in modulating their recruitment into sites of pathological vasculogenesis. Preconditioning MSCs in EGM influenced their pattern of organization into capillary-like structures, but the potential changes in the molecular marker profile for their 'switch' to the endothelial cell line remain to be evaluated.
间充质干细胞 (MSCs) 能够获得内皮样特征，但它们在调节 MSC 血管生成中的作用更为复杂。MSCs 在内皮生长培养基 (EGM) 中培养时能够表达内皮标记物，证明它们可以分化为内皮样细胞。我们的研究目的是评估 MCF-7 乳腺癌细胞系刺激常规 MSCs 和在 EGM 中培养扩增的 MSC（MSCEs）形成毛细血管样结构的能力，并评估肿瘤衍生的 VEGF 的参与。我们在 Transwell 双室培养系统中，在 VEGF、MCF-7 细胞或其条件培养基 (CM) 的存在下，将 MSCs 和 MSCEs 接种到 Matrigel 上。在培养条件下或 Transwell 系统中，MSCs 和 MSCEs 均为 CD31 阴性。MSCs 在 VEGF 或 MCF-7 细胞存在下具有明显的组织成簇和形成毛细血管样结构的趋势。MSCEs 具有相似的行为，但它们的聚类组织趋势较低。在 MCF-7 CM 的存在下，MSCs 和 MSCEs 均未形成毛细血管样结构，但 MSCs 的聚类组织趋势更强。在单独暴露于 EGM-2 以及补充有 MSCs 或 MSCEs 的 EGM-2 后，MCF-7 细胞作为贴壁细胞存在于下腔的底部，而当 MCF-7 细胞与 MSCs 共培养时，它们更倾向于作为单个细胞（而不是聚类）组织，与其他条件相比。乳腺癌细胞和 VEGF 均可刺激 MSCs 和 MSCEs 形成毛细血管样结构，表明肿瘤衍生的 VEGF 在调节它们募集到病理性血管生成部位中起作用。在 EGM 中预培养 MSCs 会影响它们形成毛细血管样结构的组织方式，但它们向内皮细胞系“转换”的分子标记谱的潜在变化仍有待评估。
