CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma. Cell Oncol (Dordr) 2020 Oct;43(5):835-845
Date
05/30/2020Pubmed ID
32468445Pubmed Central ID
PMC7581571DOI
10.1007/s13402-020-00530-8Scopus ID
2-s2.0-85085626105 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
PURPOSE: The current treatment outcomes in cholangiocarcinoma are poor with cure afforded only by surgical extirpation. The efficacy of targeting the tumoural endothelial marker CD105 in cholangiocarcinoma, as a basis for potential microbubble-based treatment, is unknown and was explored here.
METHODS: Tissue expression of CD105 was quantified using immunohistochemistry in 54 perihilar cholangiocarcinoma samples from patients who underwent resection in a single centre over a ten-year period, and analysed against clinicopathological data. In vitro flow assays using microbubbles functionalised with CD105 antibody were conducted to ascertain specificity of binding to murine SVR endothelial cells. Finally, CD105-microbubbles were intravenously administered to 10 Balb/c nude mice bearing heterotopic subcutaneous human extrahepatic cholangiocarcinoma (TFK-1 and EGI-1) xenografts after which in vivo binding was assessed following contrast-enhanced destruction replenishment ultrasound application.
RESULTS: Though not significantly associated with any examined clinicopathological variable, we found that higher CD105 expression was independently associated with poorer patient survival (median 12 vs 31 months; p = 0.002). In vitro studies revealed significant binding of CD105-microbubbles to SVR endothelial cells in comparison to isotype control (p = 0.01), as well as in vivo to TFK-1 (p = 0.02) and EGI-1 (p = 0.04) mouse xenograft vasculature.
CONCLUSION: Our results indicate that CD105 is a biomarker eminently suitable for cholangiocarcinoma targeting using functionalised microbubbles.
Author List
Nair A, Ingram N, Verghese ET, Wijetunga I, Markham AF, Wyatt J, Prasad KR, Coletta PLAuthor
Kondragunta Rajendra Prasad MBBS Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Animals
Bile Duct Neoplasms
Biomarkers, Tumor
Capillaries
Cell Line, Tumor
Cholangiocarcinoma
Endoglin
Endothelial Cells
Female
Humans
Male
Mice
Microbubbles
Microvessels
Middle Aged
Multivariate Analysis
Platelet Endothelial Cell Adhesion Molecule-1
Prognosis
Xenograft Model Antitumor Assays
