Hyaluronan (HA) and its principal receptor CD44 are known to be involved in regulating tumor cell dissemination and metastasis. It is hypothesized that the CD44-HA interaction regulates proliferation and invasion of tumor cells in dependence on the molecular weight and the presentation form of HA. To address this hypothesis, we reconstituted 3D collagen (Coll I) matrices and functionalized them with HA of molecular weight of 30-50 kDa (low molecular weight; LMW-HA) and 500-750 kDa (high molecular weight; HMW-HA). A post-modification strategy was applied to covalently immobilize HA to reconstituted fibrillar Coll I matrices, resulting in a non-altered Coll I network microstructure and stable immobilization over days. Functionalized Coll I matrices were characterized regarding topological and mechanical characteristics as well as HA amount using confocal laser scanning microscopy, colloidal probe force spectroscopy and quantitative Alcian blue assay, respectively. To elucidate tumor cell behavior, BRO melanoma cell lines with and without CD44 receptor expression were used for in vitro cell experiments. We demonstrated that only soluble LMW-HA promoted cell proliferation in a CD44 dependent manner, while HMW-HA and immobilized LMW-HA did not. Furthermore, an enhanced cell invasion was found only for immobilized LMW-HA. Both findings correlated with a very strong and specific adhesive interaction of LMW-HA and CD44+ cells quantified in single cell adhesion measurements using soft colloidal force spectroscopy. Overall, our results emphasize the importance of presentation mode and molecular weight specificity in biomaterial studies on the impact of HA on cell behavior.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:33113 |
| Date | 07 February 2019 |
| Creators | Sapudom, Jiranuwat, Ullm, Franziska, Martin, Steve, Kallbitzer, Liv, Naab, Johanna, Möller, Stephanie, Schnabelrauch, Matthias, Anderegg, Ulf, Schmidt, Stephan, Pompe, Tilo |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/acceptedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1742-7061, 10.1016/j.actbio.2016.12.026 |
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