Source : Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D

Abstract

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. The roles of HA cell surface receptors and hyaluronidases (HAses) in this process are still controversial. In order to investigate their involvement in cancer pathogenesis, we developed a reticulated HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied thirteen cell lines, from primary tumors or metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. The number of colonies, which reflects tumor cell invasiveness, ranged from 7 to 193 after 5 days of culture. Invasion was dependent on the production of HAse as well as other factors. Optimal colonization occurred when cells released HAse, lacked HA-binding sites and did not secrete HA. Moreover, we describe for the first time a HAse activity at physiological pH that may be responding to the confinement of the enzyme in a three-dimensional structure. We show here that this reticulated matrix provides a three-dimensional model for investigating mechanisms involved in malignant invasion.


gregory

gregory

Grégory MAUBON is Chief Data Officer and digital coordinator at HCS Pharma, a biotech startup focused in high content screening and complex diseases. He manages IT missions and leads digital usages linked to company needs. He is also a Augmented Reality Evangelist (presenter and lecturer) since 2008, where he created www.augmented-reality.fr and founded in 2010 RA'pro (the augmented reality promotion association). He helped many companies (in several domains) to define precisely their augmented reality needs and supported them in the implementation.

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