肝病学和胰腺科学

Are basal microvilli on the microvasculature of pancreatic ductal adenocarcinoma a tumor specific target for therapies?

Abstract

Hexige Saiyin

Pancreatic ductal adenocarcinoma (PDAC) may be a uniformly lethal malignancy with near 6 months median survival. it's a stromarich, vascular-poor and hypo-perfused tumor, which was considered to prevents efficient drug or nutrient delivery in tumor microenvironment. Paradoxically, the tumor cells have robust glucose uptake and rare necrosis, suggesting that the microvasculature has might adopted an alternate way for nutrient uptake and cellular trafficking. Using adapted thick tumor section immunostaining and three-dimensional (3D) construction imaging in human fresh tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumors; long, hair-like projections on the basal surface of micro vessels that we visit as ’basal microvilli’. Basal microvilli were also observed in intrahepatic cholangiocarcinoma (ICC) and metastatic pancreatic neuroendocrine tumor (panNET), but not in hepatocarcinoma, glioblastoma and renal clear cell carcinoma. Basal microvilli in PDAC are richer and denser than ICC and panNET. 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 tumor microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumor itself. additionally, these basal microvilli were found in regions of the tumor with low GLUT-1 expression, suggesting that their presence may be dependent upon the glucose concentration within the tumor milieu.