Serial observations on an orthotopic gastric cancer model constructed using improved implantation technique

Abstract

Aim: To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.

Methods: Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors, and the tumor tissue pieces were implanted under the serous coat. The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases.

Results: Within 2-4 wk, there were no obvious changes about the primary tumor in stomach. At the sixth week, the primary tumor began to grow fast, resulting in incrassation of the gastric wall and stenosis of the gastric cavity, and metastases into the liver and lymph nodes were detected. The tumor, which compressed the adjacent organs, gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk. There were massive metastases, and the rate of metastasis was 58% in lymph nodes, 78% in liver, 39% in kidney, and 81% in peritoneum or septum.

Conclusion: A gastric cancer model is established, which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.

Keywords: Cell line; Gastric cancer; Metastasis; Mouse model; Orthotopic implantation.

Figure 1

Macroscopic examination of the primary tumor in SGC-7901 model. The gastric cavity occupied by primary tumor was found vanished, and pylorus was obstructed totally (arrows).

Figure 2

Histopathologic structure of SGC-7901 tumors by HE staining. A: Tumor cells showed nuclear polymorphism, nuclear hyperchromatism, and much mucus in the cytoplasm (× 200); B: The primary tumor destroyed muscularis mucosae (arrows) (× 100); C: The lymph nodes were infiltrated by metastatic tumor (arrows) (× 100); D: Metastases (arrows) infiltrated into the liver (× 200); E: Metastatic tumor (arrows) invaded the kidney (× 100); F: Tumor (arrows) metastasized to the lung and surrounded bronchia or bronchiole (× 40); G: Cast-off tumor cells were detected in ascites (× 200).

Figure 3

Immunohistochemistry of SGC-7901 tumor by streptavidin-peroxidase method. Expression of Cytokeratin 20 (CK20) protein was positive, which was stained brown in the cytoplasm in the tumor of stomach (A × 40) and liver (B × 100).

Figure 4

Immunostaining of SGC-7901 tumor using streptavidin-peroxidase method. Epithelial membrane antigen signal stained brown in the cytoplasm was positive in the tumor of stomach (A × 40), lymph node (B × 40) and lung (C × 100).

Figure 5

The curve of tumor growth at different time points. The tumor volume gradually increased from the 6th wk after implantation, and reached a peak at the 12th wk.