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Flow‐regulated endothelial glycocalyx determines metastatic cancer cell activity
Author(s) -
Mensah Solomon A.,
Nersesyan Alina A.,
Harding Ian C.,
Lee Claire I.,
Tan Xuefei,
Banerjee Selina,
Niedre Mark,
Torchilin Vladimir P.,
Ebong Eno E.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901920r
Subject(s) - glycocalyx , cancer , cancer research , cell , microbiology and biotechnology , chemistry , medicine , biology , biochemistry
Cancer metastasis and secondary tumor initiation largely depend on circulating tumor cell (CTC) and vascular endothelial cell (EC) interactions by incompletely understood mechanisms. Endothelial glycocalyx (GCX) dysfunction may play a significant role in this process. GCX structure depends on vascular flow patterns, which are irregular in tumor environments. This work presents evidence that disturbed flow (DF) induces GCX degradation, leading to CTC homing to the endothelium, a first step in secondary tumor formation. A 2‐fold greater attachment of CTCs to human ECs was found to occur under DF conditions, compared to uniform flow (UF) conditions. These results corresponded to an approximately 50% decrease in wheat germ agglutinin (WGA)‐labeled components of the GCX under DF conditions, vs UF conditions, with undifferentiated levels of CTC‐recruiting E‐selectin under DF vs UF conditions. Confirming the role of the GCX, neuraminidase induced the degradation of WGA‐labeled GCX under UF cell culture conditions or in Balb/C mice and led to an over 2‐fold increase in CTC attachment to ECs or Balb/C mouse lungs, respectively, compared to untreated conditions. These experiments confirm that flow‐induced GCX degradation can enable metastatic CTC arrest. This work, therefore, provides new insight into pathways of secondary tumor formation.