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Göteborgs universitets publikationer

Spatial proteomic analysis of GOT1 human small intestine neuroendocrine tumor in nude mice following 177Lu-octreotate therapy

Författare och institution:
Johan Spetz (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik & Sahlgrenska Cancer Center); Mikael Montelius (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik); Maria Ljungberg (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik); Khalil Helou (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för onkologi & Sahlgrenska Cancer Center); Eva Forssell-Aronsson (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik & Sahlgrenska Cancer Center)
Publicerad i:
62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016,
Publikationstyp:
Konferensbidrag - refereegranskat abstract
Publiceringsår:
2016
Språk:
engelska
Sammanfattning (abstract):
Background: 177Lu-octreotate can be used for therapy of somatostatin receptor expressing neuroendocrine tumors (NET). 177Lu-octreotate therapy has achieved high cure rates in GOT1 (human small intestine NET) transplanted to nude mice. However, clinical studies result in moderate response, and complete tumor remission is rarely seen. Solid tumors often develop necrotic cores during growth due to e.g. insufficient vascularization, which may account for the different uptake kinetics and varying therapeutic success seen after 177Lu-octreotate treatment. It is therefore important to explore the cellular effects of 177Lu-octreotate to further optimize treatment parameters and identify biomarkers for treatment response assessment. Aim: To detect significant changes in protein profiles from peripheral and central samples of GOT1 tumor after 177Lu-octreotate therapy. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate (corresponding to 4 Gy tumor absorbed dose) and killed after 13 days. Total cellular proteins were extracted from the peripheral and central parts of surgically excised tumor samples. Proteomic profiling was generated using liquid chromatography tandem-mass spectrometry (LC-MS/MS), followed by database-based protein identification and relative quantification. Functional annotation of proteins was performed using the DAVID bioinformatics resource tool. Results: The LC-MS/MS analysis identified 58 differentially expressed proteins (p<0.05, Fold Change>1.2) between the peripheral and central parts of tumor samples. Forty of these showed higher levels in the peripheral compared with the central samples, and among them were proteins associated with blood vessel/vasculature development (e.g. FAK1, H6ST1, LMA4, and SYWM), regulation of cell cycle and apoptosis (e.g. FAK1 and MK01), and cellular integrity (e.g. PDLI5, CALD1, FERM2, and NEB2). Conclusions: Taken together, these findings suggest spatial differences in tumor response to 177Lu-octreotate, mainly constituted by differences in vascularization and cellular integrity. These findings indicate potential venues for prognostic evaluation of NET therapy using 177Lu-octreotate. However, further studies are needed to determine whether these effects are time- and/or dose-dependent.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
NATURVETENSKAP ->
Biologiska vetenskaper ->
Bioinformatik och systembiologi
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper ->
Cell- och molekylärbiologi
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper ->
Mikrobiologi inom det medicinska området ->
Mikrobiologi ->
Medicinsk mikrobiologi
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Cancer och onkologi
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Radiologi och bildbehandling ->
Radiofysik
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Radiologi och bildbehandling ->
Strålningsbiologi
Postens nummer:
237827
Posten skapad:
2016-06-17 09:00

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