Real-time bioluminescence and tomographic imaging of gastric cancer in a novel orthotopic mouse model

Abstract

Abstract. Gastric cancer is the second leading cause of cancer mortality worldwide. Understanding the multistep process of carcinogenesis of gastric cancer is pivotal to develop novel therapeutic strategies. Molecular imaging in preclinical cancer models bridges the gap of laboratory-based experiment and clinical translation. To this end, the human gastric cancer cell line SGC-7901 was established to stably express luciferase and GFP by lentiviral transduction (SGC7901-Luc-GFP). Preclinical models were developed by orthotopic transplantation of SGC-7901-Luc-GFP into the sub-serosal layer of the stomach of immunocompromised mice. Tumor progression and therapeutic responses were dynamically tracked by bioluminescence imaging (BLI). Bioluminescence tomography (BLT) was used to monitor stereoscopic morphological and signal changes during tumor progression. Good correlation between cell number and bio luminescence/ fluorescence intensity was observed (R 2 =0.9983/r 2 =0.9974) in vitro. Tumor progression and therapeutic response could be successfully followed directly by BLI. Importantly, BLT provided a more accurate spatial location and tomographic quantification of the internal lesion. In conclusion, our novel bioluminescence-based preclinical gastric cancer models enable superior, noninvasive monitoring gastric cancer progression and their drug responses. The BLT technique in particular, may have great potential for future oncological studies.

An orthotopic mouse model of gastric cancer invasion and metastasis

“…Our study shows that mouse weight did not differ between tumour bearing and non-bearing mice even once tumours and metastasis were well established. During the experimental duration, mice appeared healthy and active with no evidence of cachexia and lethargy which was observed in other studies 25 . Due to extensive tumour infiltration into the stomach it was not possible to determine tumour weight even at the time of autopsy.…”

AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

“…After xenografts were grown in the mice for five generations, they were transplanted into the subserosa of the greater gastric curvature and observed for metastasis. This is an orthotopic mouse model that mimics gastric cancer metastasis, including lymph node and peritoneal transplantation metastases 37, 49. Using the AEG‐1 stable knockdown cell lines in this model, we revealed that silencing of AEG‐1 expression not only inhibited tumour growth in parallel with decreased expression of eIF4E, MMP‐9 and Twist, but it also inhibited the lymph node and peritoneal metastasis of gastric cancer.…”

“…As inoculating SGC7901 cells directly to the subserosal layer of the greater gastric curvature results in almost negative lymph node or peritoneal metastasis, we used a model reported by Hu et al . 37 Briefly, SGC7901‐AEG‐1_shRNA cells with stable AEG‐1 silencing and the control SGC7901‐scramble_shRNA cells were inoculated subcutaneously into the flank region of nude mice to establish a xenograft mouse model. When the diameter of the xenografts reached 5 mm, tumours were isolated and sheared into 1–2 mm 3 pieces.…”

“…This orthotopic model was previously described by Hu et al . 37. Tissue samples were fixed in 10% formalin and embedded in paraffin.…”

Hybrid radiosity-SP3 equation based bioluminescence tomography reconstruction for turbid medium with low- and non-scattering regions

“…Finally, the incision in the abdominal wall and skin was closed with Prolene suture. 21 One week after the SGC7901-Luc-GFP cells were inoculated, 8 mg/kg docetaxel (Taxotere, Sanofi-Aventis) or 0.9% saline was assigned to the gastric cancer-bearing mouse for treatment once a week. After 3 weeks of treatment, filtersterilized D-luciferin solution (150 mg/kg body weight) was injected into the mouse peritoneal cavity 10 min prior to bioluminescent image acquisition.…”