Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma

Hexige Saiyin, Christine M. Ardito-Abraham, Yanhua Wu, Youheng Wei, Yuan Fang, Xu Han, Jianang Li, Ping Zhou, Qing Yi, Anirban Maitra, Jun O. Liu, David A. Tuveson, Wenhui Lou, Long Yu

Research output: Contribution to journalArticle

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three-dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair-like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo- and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumours.

Original languageEnglish (US)
Pages (from-to)142-154
Number of pages13
JournalJournal of Pathology
Volume236
Issue number2
DOIs
StatePublished - Jun 1 2015

Keywords

  • 3D imaging
  • basal microvilli
  • microvessels
  • neoplasia
  • pancreas

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Saiyin, H., Ardito-Abraham, C. M., Wu, Y., Wei, Y., Fang, Y., Han, X., Li, J., Zhou, P., Yi, Q., Maitra, A., Liu, J. O., Tuveson, D. A., Lou, W., & Yu, L. (2015). Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma. Journal of Pathology, 236(2), 142-154. https://doi.org/10.1002/path.4506