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Analysis of Cell Migration within a Three-dimensional Collagen Matrix
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Cancer cell migration in collagen-hyaluronan composite extracellular matrices.

Shalini R Unnikandam Veettil1, Dohgyu Hwang2, Jacinta Correia3

  • 1Department of Chemical and Biological Engineering, Iowa State University, United States.

Acta Biomaterialia
|June 11, 2021
PubMed
Summary

Hyaluronan (HA) in the tumor microenvironment affects cancer cell migration and matrix remodeling. High molecular weight HA decreases cell migration and increases extracellular matrix contraction, impacting cancer progression and drug delivery.

Keywords:
CompactionGlycationHyaluronateHyaluronic acidMDA-MB-231StiffnessStress relaxation

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Area of Science:

  • Biophysics
  • Cancer Biology
  • Biomaterials Science

Background:

  • Hyaluronan (HA) is a crucial component of the tumor microenvironment (TME), influencing cancer growth and invasiveness.
  • Elevated HA levels in the TME can impede drug delivery, and its degradation via hyaluronidases (HYALs) is explored for therapeutic benefit.
  • The specific effects of altered HA molecular weight (MW) and concentration on TME biophysical properties and cancer cell behavior remain largely unknown.

Purpose of the Study:

  • To investigate the influence of HA molecular weight and concentration on the biophysical properties of the tumor microenvironment.
  • To correlate changes in HA's mechanical and structural properties with cancer cell migration and extracellular matrix (ECM) remodeling.
  • To elucidate the biological consequences of HA degradation in the TME, particularly concerning cancer cell behavior.

Main Methods:

  • Utilized very low (vLMW), low (LMW), and high molecular weight (HMW) HA at various physiologically relevant concentrations.
  • Quantified changes in HA-collagen composite networks, including elastic modulus, collagen network pore size, and collagen fiber diameter.
  • Assessed cell migration and ECM remodeling using gel compaction assays in 3D TME-mimicking environments.

Main Results:

  • Increasing HA concentration elevated elastic modulus, collagen network pore size, and collagen fiber diameter.
  • Despite increased pore size, HA molecules sterically hindered cell migration, leading to decreased movement with higher HA concentrations.
  • High molecular weight HA, particularly at high concentrations, significantly increased ECM compaction, an effect not observed in HA-free collagen gels of similar stiffness.

Conclusions:

  • Hyaluronan molecular weight and concentration significantly modulate the mechanical and structural properties of the TME.
  • Steric hindrance by HA molecules plays a critical role in regulating cancer cell migration.
  • High molecular weight HA can promote ECM contraction, suggesting a complex role in cancer progression and potential implications for therapies targeting HA degradation.