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Investigation of the effect of structured hyaluronic acid surfaces on cell proliferation and expression of HA cellular receptors:CD44 and RHAMM

By Ana Catia Ferrao Marques

Abstract

Hyaluronic acid (HA) is one of the major components of the extracellular matrix; and may exhibit different biological functions, dependent on polymer molecular weight (MW). The signalling events performed by HA are mediated through interactions with its main cell receptors: CD44 and RHAMM. However, the direct effect between the HA MW and the expression of CD44 and RHAMM remains unclear. This study aimed to investigate whether different HA polymer MW alters the proliferation of tumour-derived cell lines, and whether different HA-sized has an effect on the regulation of the expression of CD44 and RHAMM. In order to determine size-specific responses of tumour cells of defined fragment MW, this investigation was undertaken using HA-tethered culture surfaces. Four surfaces were constructed, coated with polymers of different MWs. HA (4, 234, 2590 kDa) and an oligomer mixture were tethered onto an aminosilane (AHAPTMS)-treated glass surfaces using a carbodiimide reaction. Surfaces were analysed using a toolbox of in situ characterisation techniques, including wettability measurements, QCM, AFM and confocal microscopy. Using the constructed surfaces was demonstrated that HA-polymer MW modulates cell proliferation of human bladder (RT112 and T24) and prostate (PC3 and PNT1A) cell lines, with low HA MW (HA4) increasing proliferation, whereas a decrease is seen in the presence of medium (HA234) and high MW fragments (HA2590). The proliferation stimulus performed by HA was found to be phenotype dependent, with HA4 surfaces stimulating an increased proliferation in those less invasive cell lines (T24 and PNT1A), while HA234 and HA2590 inducing a sharper decrease in the most malignant tumour cell lines (RT112 and PC3). It was also demonstrated that the regulation of CD44 and RHAMM transcripts expression appears to be phenotype dependent but not HA-MW dependent. HA down-regulates CD44 and RHAMM in the most malignant cell lines; with up-regulation of the expression of the cell receptors in the less invasive cell lines. In addition, the presence of exogenous HA was shown to be involved in the regulation of the expression of CD44 variants expression. The results obtained for the CD44 and RHAMM protein expression were also found to be correlated with the obtained transcripts expression. However, the significance of these findings in tumourigenesis remains unclear. Findings from this investigation may help in the design and development of biocompatible implants with controlled surface properties to be used in cancer therapeutics; with medium and large HA polysaccharides being potential biopolymer candidates, useful for the development of novel therapies for highly invasive cancer. In addition, implications from this work can serve as a base for future research, and can lead to ideas for drugs and methods to be used in cancer therapeutic approaches

Topics: CD44, extracellular matrix, hyaluronic acid, proliferation, RHAMM, surface, tumour
Publisher: Cranfield University
Year: 2011
OAI identifier: oai:dspace.lib.cranfield.ac.uk:1826/6859
Provided by: Cranfield CERES

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  1. 09/23/97 Change QATM 130 to 229. Change lower limit of intrinsic viscosity from 14 to 20.
  2. 57439 04/30/01 Add new test method QATM 256. Remove record retention section. Update references. Remove VOC testing.
  3. Add 260nm to Nucleic Acid Test.
  4. Add specification for viscosity in 0.9% saline. 14358 02/19/97 Add Lifecore part number and remove SPEC 801 requirement. Change bioburden, protein, and ethanol for specifications. Change viscosity on 3% . Add expiration date.
  5. Add streptococcus pyogenes to microbial identification. doi
  6. Add Volatile Organic Compounds Testing. 56502 8/21/00 Chang QATM’s 060, 251, and 033 to Sop 9011. Update references. Change word to read mean not average.
  7. change nucleic acid <0.5 absorbance to,
  8. Change title of QATM 001 in references section.
  9. No changes were made to test specifications
  10. Remove reference to QATM 037, add reference to
  11. Remove reference to SOP 1341, add MPR 0059.

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