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Noninvasive intravital high-resolution imaging of pancreatic neuroendocrine tumours

Balan, Mirela; Trusohamn, Marta; Ning, Frank Chenfei; Jacob, Stefan; Pietras, Kristian LU ; Eriksson, Ulf; Berggren, Per Olof and Nyqvist, Daniel (2019) In Scientific Reports 9(1). p.14636-14636
Abstract

Preclinical trials of cancer drugs in animal models are important for drug development. The Rip1Tag2 (RT2) transgenic mouse, a model of pancreatic neuroendocrine tumours (PNET), has provided immense knowledge about PNET biology, although tumour progression occurs in a location inaccessible for real-time monitoring. To overcome this hurdle we have developed a novel platform for intravital 3D imaging of RT2 tumours to facilitate real-time studies of cancer progression. Pre-oncogenic islets retrieved from RT2 mice were implanted into the anterior chamber of the eye (ACE) of host mice, where they engrafted on the iris, recruited blood vessels and showed continuous growth. Noninvasive confocal and two-photon laser-scanning microscopy through... (More)

Preclinical trials of cancer drugs in animal models are important for drug development. The Rip1Tag2 (RT2) transgenic mouse, a model of pancreatic neuroendocrine tumours (PNET), has provided immense knowledge about PNET biology, although tumour progression occurs in a location inaccessible for real-time monitoring. To overcome this hurdle we have developed a novel platform for intravital 3D imaging of RT2 tumours to facilitate real-time studies of cancer progression. Pre-oncogenic islets retrieved from RT2 mice were implanted into the anterior chamber of the eye (ACE) of host mice, where they engrafted on the iris, recruited blood vessels and showed continuous growth. Noninvasive confocal and two-photon laser-scanning microscopy through the transparent cornea facilitated high-resolution imaging of tumour growth and angiogenesis. RT2 tumours in the ACE expanded up to 8-fold in size and shared hallmarks with tumours developing in situ in the pancreas. Genetically encoded fluorescent reporters enabled high-resolution imaging of stromal cells and tumour cell migration. Sunitinib treatment impaired RT2 tumour angiogenesis and growth, while overexpression of the vascular endothelial growth factor (VEGF)-B increased tumour angiogenesis though tumour growth was impaired. In conclusion, we present a novel platform for intravital high-resolution and 3D imaging of PNET biology and cancer drug assessment.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
pages
14636 - 14636
publisher
Nature Publishing Group
external identifiers
  • scopus:85073103802
ISSN
2045-2322
DOI
10.1038/s41598-019-51093-0
language
English
LU publication?
yes
id
884e0d1b-60c5-4698-8b0f-0ca4bf75b910
date added to LUP
2019-10-21 15:00:08
date last changed
2019-10-29 05:57:51
@article{884e0d1b-60c5-4698-8b0f-0ca4bf75b910,
  abstract     = {<p>Preclinical trials of cancer drugs in animal models are important for drug development. The Rip1Tag2 (RT2) transgenic mouse, a model of pancreatic neuroendocrine tumours (PNET), has provided immense knowledge about PNET biology, although tumour progression occurs in a location inaccessible for real-time monitoring. To overcome this hurdle we have developed a novel platform for intravital 3D imaging of RT2 tumours to facilitate real-time studies of cancer progression. Pre-oncogenic islets retrieved from RT2 mice were implanted into the anterior chamber of the eye (ACE) of host mice, where they engrafted on the iris, recruited blood vessels and showed continuous growth. Noninvasive confocal and two-photon laser-scanning microscopy through the transparent cornea facilitated high-resolution imaging of tumour growth and angiogenesis. RT2 tumours in the ACE expanded up to 8-fold in size and shared hallmarks with tumours developing in situ in the pancreas. Genetically encoded fluorescent reporters enabled high-resolution imaging of stromal cells and tumour cell migration. Sunitinib treatment impaired RT2 tumour angiogenesis and growth, while overexpression of the vascular endothelial growth factor (VEGF)-B increased tumour angiogenesis though tumour growth was impaired. In conclusion, we present a novel platform for intravital high-resolution and 3D imaging of PNET biology and cancer drug assessment.</p>},
  author       = {Balan, Mirela and Trusohamn, Marta and Ning, Frank Chenfei and Jacob, Stefan and Pietras, Kristian and Eriksson, Ulf and Berggren, Per Olof and Nyqvist, Daniel},
  issn         = {2045-2322},
  language     = {eng},
  number       = {1},
  pages        = {14636--14636},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Noninvasive intravital high-resolution imaging of pancreatic neuroendocrine tumours},
  url          = {http://dx.doi.org/10.1038/s41598-019-51093-0},
  volume       = {9},
  year         = {2019},
}