Abstract
Cancer stem cells (CSCs), a small population of cancer cells, have been considered to be the origin of cancer initiation, recurrence, and metastasis. Tumor microenvironment provides crucial signals for CSCs to maintain stem cell properties and promotes tumorigenesis. Therefore, establishment of an appropriate cell culture system to mimic the microenvironment for CSC studies is an important issue. In this study, we grew colon and hepatocellular carcinoma (HCC) cells on chitosan membranes and evaluated the tumor progression and the CSC properties. Experimental results showed that culturing cancer cells on chitosan increased cell motility, drug resistance, quiescent population, self-renewal capacity, and the expression levels of stemness and CSC marker genes, such as OCT4, NANOG, CD133, CD44, and EpCAM. Furthermore, we demonstrated that chitosan might activate canonical Wnt/β-catenin-CD44 axis signaling in CD44positive colon cancer cells and noncanonical Wnt-STAT3 signaling in CD44negative HCC cells. In conclusion, chitosan as culture substrates activated the essential signaling of CSCs and promoted CSC properties. The chitosan culture system provides a convenient platform for the research of CSC biology and screening of anticancer drugs.
Highlights
Cancer is one of the major leading causes of death worldwide and associated with mortality and morbidity[1]
We showed that chitosan itself promoted Cancer stem cells (CSCs)-related characteristics and tumor progression of CD44positive colon cancer cells and CD44negative hepatocellular carcinoma (HCC) cells
To investigate how CS and CSHA membranes directly affect the phenotypes of colon cancer cell lines HT29, DLD-1, HCT116, SW480 and HCC cell lines Huh[7], HepG2, Hep3B, SKHep-1, we cultured the cells on membranes for 72 hrs following observation per 24 hrs
Summary
Cancer is one of the major leading causes of death worldwide and associated with mortality and morbidity[1]. They share some similar properties with stem cells and are named as cancer stem cells (CSCs)[2,3] These cells possess higher migration ability that is associated with invasion and metastasis[4]. Rao et al recently demonstrated that chitosan nanoparticles could bind CSCs via CD44 receptor, a major target gene of Wnt signaling[30,31]. This finding implied that the chemical properties of chitosan might resemble HA to some extent. We unraveled the mechanisms regarding how chitosan substrates promoted cancer stemness and revealed that canonical and noncanonical Wnt signaling pathways played key roles in the interactions between chitosan and cancer cells. Chitosan as culture substrates may provide a convenient platform that mimics ECM for the research of CSC biology and drug screening
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