Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Finland.
Biocenter Oulu Electron Microscopy Core Facility, University of Oulu, Oulu, Finland.
Exp Cell Res. 2020 Apr 1;389(1):111885. doi: 10.1016/j.yexcr.2020.111885. Epub 2020 Feb 1.
The interaction between squamous cell carcinoma (SCC) cells and the tumor microenvironment (TME) plays a major role in cancer progression. Therefore, understanding the TME is essential for the development of cancer therapies. We used four (primary and metastatic) head and neck (HN) SCC cell lines and cultured them on top of or within 5 matrices (mouse sarcoma-derived Matrigel®, rat collagen, human leiomyoma-derived Myogel, human fibronectin and human fibrin). We performed several assays to study the effects of these matrices on the HNSCC behavior, such as proliferation, migration, and invasion, as well as cell morphology, and molecular gene profile. Carcinoma cells exhibited different growth patterns depending on the matrix. While fibrin enhanced the proliferation of all the cell lines, collagen did not. The effects of the matrices on cancer cell migration were cell line dependent. Carcinoma cells in Myogel-collagen invaded faster in scratch wound invasion assay. On the other hand, in the spheroid invasion assay, three out of four cell lines invaded faster in Myogel-fibrin. These matrices significantly affected hundreds of genes and a number of pathways, but the effects were cell line dependent. The matrix type played a major role in HNSCC cell phenotype. The effects of the ECMs were either constant, or cell line dependent. Based on these results, we suggest to select the most suitable matrix, which provides the closest condition to the in vivo TME, in order to get reliable results in in vitro experiments.
鳞状细胞癌 (SCC) 细胞与肿瘤微环境 (TME) 的相互作用在癌症进展中起着重要作用。因此，了解 TME 对于癌症治疗的发展至关重要。我们使用了四种（原发性和转移性）头颈部 (HN) SCC 细胞系，并将它们培养在五种基质（鼠肉瘤衍生的 Matrigel®、大鼠胶原、人平滑肌瘤衍生的 Myogel、人纤维连接蛋白和人纤维蛋白）的顶部或内部。我们进行了多项实验来研究这些基质对 HNSCC 行为的影响，例如增殖、迁移和侵袭，以及细胞形态和分子基因谱。癌细胞根据基质呈现出不同的生长模式。虽然纤维蛋白增强了所有细胞系的增殖，但胶原蛋白没有。基质对癌细胞迁移的影响取决于细胞系。Myogel-胶原中的癌细胞在划痕侵袭实验中更快地迁移。另一方面，在球体侵袭实验中，四种细胞系中的三种在 Myogel-纤维蛋白中更快地侵袭。这些基质显著影响了数百个基因和许多途径，但影响取决于细胞系。基质类型在 HNSCC 细胞表型中起着重要作用。细胞外基质的影响要么是恒定的，要么是依赖于细胞系的。基于这些结果，我们建议选择最适合的基质，为体外实验提供最接近体内 TME 的条件，以获得可靠的结果。
