Human Colorectal Cancer Infrastructure Constructed by the Glycocalyx.

Masahito Tachi,Hiroyuki Tomita,Shinji Ogura,Hideki Mori,Genzou Takemura,Kazuhiro Yoshida,Kodai Suzuki,Takuji Tanaka,Hideshi Okada,Ayumi Niwa,Hirotsugu Fukuda,Nobuhisa Matsuhashi,Akira Hara

doi:10.3390/jcm8091270

Masahito Tachi, Hiroyuki Tomita + Show 11 more

Open Access

https://doi.org/10.3390/jcm8091270

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Abstract

Cancer cells can survive and grow via angiogenesis. An alternative but controversial theory is cancer cells may grow via vasculogenic mimicry (VM), in which the cancer cells themselves construct vessel-like channels that are considered a leading cause of drug resistance. The dynamic functions of the glycocalyx (GCX), a meshwork composed of proteoglycans and glycoproteins that surrounds cell membranes, have been observed in endothelial cells within tumors. However, the actual structural shape formed by the GCX in human patients remains unclear. Here, we visualized the three-dimensional (3D) network structure constructed by bulky GCX in human colorectal cancer (CRC) patients using scanning electron microscopy with lanthanum nitrate staining. The network structure extended throughout the cancer cell nest, opening into capillaries, with a tunnel channel that exhibited a net- and spongy-like ultrastructure. The expression of endothelial and cancer-specific GCX-binding lectins was dramatically increased in the interstitial spaces between cancer cells. Even accounting for the presence of artifacts resulting from sample preparation methods, the intercellular tunnels appeared to be coated with the bulky GCX. Further, this 3D network structure was also observed in the tumors of ApcMin/+ mice. In conclusion, the bulky GCX modifies the network structure of CRCs in human and mice.

Highlights

Cancer cells survive by adapting to their changing environment, and require oxygen and nutrients supplied through blood vessels to rapidly proliferate [1]
Human colorectal cancer (CRC) specimens were evaluated for vasculogenic mimicry (VM) formation, which is typically defined as the presence of channels lined with CD31− and Periodic Acid-Schiff (PAS)+ cancer cells, as determined by double staining (Figure 1b)
The 3D tunnel channel structure was constructed through the bulkiness of GCX. These results suggest that the wide intercellular tunnels may be maintained with collagen fibers and coated with bulky GCX in patient-derived CRC compared with normal epithelium; we are currently confirming if the obtained scanning electron microscope (SEM) images were real and true through ongoing experiments

Summary

Introduction

Cancer cells survive by adapting to their changing environment, and require oxygen and nutrients supplied through blood vessels to rapidly proliferate [1]. VM is a blood supply system composed of cancer cells themselves, independent of endothelial vessels [2,3]. Hydrated gel-like layers (approximately 50–500 nm), called the glycocalyx (GCX), coat the surfaces of endothelial cells in the blood vessel lumen and are composed of glycolipids, glycoproteins, and proteoglycans [6]. Endothelial GCX has multiple functions, including mechanosensing and signal transduction, prevention of leukocyte adhesion and extravasation, modulation of shear stress on the plasma membrane, and regulation of the selective permeability barrier function of the structure [6], and is associated with many human diseases, including cancer [7,8]

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