Related Experiment Video
Updated: Jan 26, 2026
Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
Published on: June 15, 2019
Evaluating the Efficiency of Hyaluronic Acid for Tumor Targeting via CD44
Alice Spadea1,2,3, Julio Manuel Rios de la Rosa1,2,4, Annalisa Tirella1,2
1Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health , University of Manchester and Manchester Academic Health Science Centre , Stopford Building , Manchester M13 9PT , U.K.
Abstract:
The development of delivery systems capable of tumor targeting represents a promising strategy to overcome issues related to nonspecific effects of conventional anticancer therapies. Currently, one of the most investigated agents for cancer targeting is hyaluronic acid (HA), since its receptor, CD44, is overexpressed in many cancers. However, most of the studies on CD44/HA interaction have been so far performed in cell-free or genetically modified systems, thus leaving some uncertainty regarding which cell-related factors influence HA binding and internalization (collectively called "uptake") into CD44-expressing cells. To address this, the expression of CD44 (both standard and variants, designated CD44s and CD44v, respectively) was evaluated in human dermal fibroblasts (HDFs) and a large panel of cancer cell lines, including breast, prostate, head and neck, pancreatic, ovarian, colorectal, thyroid, and endometrial cancers. Results showed that CD44 isoform profiles and expression levels vary across the cancer cell lines and HDF and are not consistent within the cell origin. Using composite information of CD44 expression, HA binding, and internalization, we found that the expression of CD44v can negatively influence the uptake of HA, and, instead, when cells primarily expressed CD44s, a positive correlation was observed between expression and uptake. In other words, CD44shigh cells bound and internalized more HA compared to CD44slow cells. Moreover, CD44shigh HDFs were less efficient in uptaking HA compared to CD44shigh cancer cells. The experiments described here are the first step toward understanding the interplay between CD44 expression, its functionality, and the underlying mechanism(s) for HA uptake. The results show that factors other than the amount of CD44 receptor can play a role in the interaction with HA, and this represents an important advance with respect to the design of HA-based carriers and the selection of tumors to treat according to their CD44 expression profile.
Insights
Hyaluronic acid (HA) uptake by CD44-expressing cells is influenced by CD44 variants (CD44v) and standard (CD44s) expression levels. CD44s promotes HA uptake, while CD44v can hinder it, impacting cancer targeting strategies.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Drug Delivery Systems
Background:
- Tumor-targeted delivery systems are crucial for improving anticancer therapy efficacy and reducing side effects.
- Hyaluronic acid (HA) is a key agent for cancer targeting due to CD44 receptor overexpression in many cancers.
- Understanding cell-related factors influencing HA uptake by CD44-expressing cells is vital for optimizing targeted therapies.
Purpose of the Study:
- To investigate how CD44 standard (CD44s) and variant (CD44v) isoforms affect hyaluronic acid (HA) binding and internalization (uptake) in various cancer cell lines and human dermal fibroblasts (HDFs).
- To determine the correlation between CD44 expression levels, CD44 isoform profiles, and HA uptake efficiency.
- To identify factors beyond CD44 receptor quantity that influence HA-cell interactions for improved design of HA-based drug delivery systems.
Main Methods:
- Evaluated CD44 standard (CD44s) and variant (CD44v) expression across a panel of human cancer cell lines (breast, prostate, head and neck, pancreatic, ovarian, colorectal, thyroid, endometrial) and human dermal fibroblasts (HDFs).
- Assessed hyaluronic acid (HA) binding and internalization (uptake) in these cell lines.
- Correlated CD44 expression profiles and levels with observed HA uptake efficiency.
Main Results:
- CD44 isoform expression and levels varied significantly among different cancer cell lines and HDFs, and were not consistent based on cell origin.
- Expression of CD44 variant (CD44v) isoforms was found to negatively influence HA uptake.
- Higher expression of CD44 standard (CD44s) isoforms correlated positively with increased HA binding and internalization, particularly in cancer cells compared to HDFs.
Conclusions:
- CD44 standard (CD44s) expression positively correlates with hyaluronic acid (HA) uptake, whereas CD44 variant (CD44v) expression can impede it.
- HA uptake efficiency is influenced by factors beyond just the total amount of CD44 receptor, including the specific CD44 isoform profile.
- These findings are critical for designing effective HA-based drug delivery systems and selecting appropriate tumor types for targeted therapy based on their CD44 expression characteristics.
Related Concept Videos
03:42Amino acids
03:27Mixtures of Acids
A Mixture of a Strong Acid and a Weak Acid
In a mixture of a strong acid and a weak acid, the strong acid dissociates completely and becomes a source of almost all the hydronium ions...
03:38Polyprotic Acids
02:43Nucleic acids
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
02:43Nucleic Acids
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
01:21Acidity of Carboxylic Acids