Forsøksdyr: In Vivo imaging of small cell lung cancer (SCLC) metastases

Godkjenningsdato 05.11.2020

Godkjenningsperiode 05.11.2020-05.11.2022

1 Formål
Globally, lung cancer is the leading cause of cancer-related deaths. Small cell lung cancer (SCLC) accounts for 15–20 % of all lung cancer cases. The capacity of SCLC to rapidly and extensively metastasise is a main reason for its high mortality rate (5-year relative survival rate for SCLC patients is 6%). To improve treatment for these patients it is essential to consider strategies to block the metastatic potential of SCLC.
A particular region of chromosome 3 is hetero- or homozygously deleted in this subtype of lung cancers that are particularly metastatic and lethal (small cell lung cancer, SCLC). Thus it is believed that this region harbors one or more tumor suppressor genes important for SCLC progression.
Recently, our group functionally characterised one of the unstudied candidates, tumor suppressor genes in this region (NAA80), and revealed that this gene controls cytoskeleton dynamics and strongly limits cell motility. The aim of this study is to reveal the impact of this gene in SCLC metastasis in vivo, by the use of an orthotopic model where two different SCLC cells (+/-gene introduced +luciferase) will be injected into the lung parenchyma of immune-deficient mice. Tumor growth and metastasis will be monitored by weekly whole body bioluminescence imaging.

2 Skadevirkninger
For the orthotopic implantation of tumor cells, a minor surgical procedure under general anaesthesia, will be performed. Mice will develop lung cancer and metastases, but they will be euthanised before the general condition will be impaired. For this reason, we considered the experiment as being of moderate severity.

3 Forventet nytteverdi
The proposed experiment will, if successful, define an important factor for SCLC metastasis and open up new options for drug development and disease treatment. Gene status may also be useful as a biomarker for metastatic cancers.

4 Antall dyr og art
66 immuno-deficient mice

5 Hvordan etterleve 3R
The main objective of the experiment is to identify if NAA80 gene deficiency has an impact on tumor growth and metastases in vivo. Tumor development and metastatic spread cannot be tracked in vitro.
The smallest possible groups to provide a statistically significant power will be used.
The implantation of cancer cells will be achieved under anaesthesia. The animals will receive analgesia pre and post implantation and will be followed up closely by project members. Experienced technicians will monitor the animals and they will very early discover any sign of illness and take the decision of euthanasia, if necessary. All cages will have environmental enrichment available at Vivarium.