Gastro-Enteropancreatic Neuroendocrine Tumor Cell Dynamics in Liver Microvasculature.
For many cancers, liver metastasis is common and usually indicates poor prognosis. Gastro-enteropancreatic neuroendocrine tumors (GEPNETs) of the midgut are a heterogeneous group of cancers that typically remain asymptomatic until they metastasize to the liver. However, the mechanisms by which these usually indolent cancers establish distal metastasis remain unclear. To begin to elucidate this process, we performed standard in vitro assays to assess cell motility, transendothelial migration, and invasion using BON cells, a widely used model GEPNET cell line. In addition, transmission electron microscopy was used in combination with a novel ex vivo organ slice xenograft model to reveal ultrastructural details of the initial events of BON cell extravasation and re-distribution within the liver. The ultrastructural resolution of the extravasation process revealed the route, sequence, and time course by which tumor cells migrated from the sinusoidal lumen into the hepatic parenchyma in this organ slice model. Both standard in vitro assays and our organ slice model indicated that tumor cells migrated through the discontinuous sinusoidal endothelium to invade the liver parenchyma.
1Department of Neurosciences,University of Toledo Medical Center,3000 Arlington Avenue,Toledo,OH 43614-2598,USA.
Priyodarshan
P
Goswamee
1Department of Neurosciences,University of Toledo Medical Center,3000 Arlington Avenue,Toledo,OH 43614-2598,USA.
Sasi
S
Arunachalam
1Department of Neurosciences,University of Toledo Medical Center,3000 Arlington Avenue,Toledo,OH 43614-2598,USA.
Saurabh
S
Mehta
3Department of Pharmacology,Peshawar Medical College,Warsak Road Peshawar,Khyber Pakhtunkhwa 25160,Pakistan.
Riaz
R
Nasim
2Department of Pathology,University of Toledo Medical Center,3000 Arlington Avenue,Toledo,OH 43614-2598,USA.
William T
WT
Gunning
1Department of Neurosciences,University of Toledo Medical Center,3000 Arlington Avenue,Toledo,OH 43614-2598,USA.
David R
DR
Giovannucci
D000818:Animals; D002465:Cell Movement; D007414:Intestinal Neoplasms / Q000473:pathology* / Q000556:secondary*; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000473:pathology*; D008962:Models, Theoretical; D018358:Neuroendocrine Tumors / Q000473:pathology* / Q000556:secondary*; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000556:secondary*; D013274:Stomach Neoplasms / Q000473:pathology* / Q000556:secondary*; D013997:Time Factors
GEPNET; extravasation; liver metastasis; organotypic slice; ultrastructure