Gastric Xenograft Models

Altogen Labs validated Gastric Cancer Xenograft animal models:

NCI-N87,  SGC-7901,  HS746T,  AGS,  MKN-45,  SNU5,  SNU-16

Stomach cancer, or gastric cancer, often develops in the stomach lining. Symptoms include weight loss, difficulty swallowing, bloody stools, nausea, vomiting, yellowing of the skin and whites of eyes, heartburn and weight loss. The most common cause of gastric cancer is infection by Helicobacter pylori, but other risk factors include smoking, diet and inherited genetic risk factors (CDH1 mutation). Diagnosis often involves a CT scan or gastroscopic exam, although there was a 2013 study where a breathalyzer exam was successful in gastric cancer diagnosis. There are several types of stomach cancer including adenocarcinomas (most common), lymphomas, gastrointestinal stromal tumors (GIST), carcinoid and mesenchymal tumors. Diffuse adenocarcinomas, or linitis plastica, are not cohesive tumor cells and secret mucus delivered in the interstitum and are poorly differentiated. Intestinal adenocarcinomas have irregular tubular structures and often invade the gastric wall. Carcinoid tumors start in the hormone-producing stomach cells and are generally slow growth with a low metastasis rate. GIST for from interstitial cells of Cajal, which signal the digestive tract muscles to contract. There are five layers that make up the stomach starting with the innermost mucosa, then submucosa, muscularis propria, subserosa and serosa; many adenocarcinomas are classified based on which layers have been affected or invaded by the tumor. Testing for carcinoembryonic antigen (CEA) and carbohydrate antigen (CA), well-known tumor markers, can help determine the extent of staging and metastasis. Treatment includes endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), chemotherapy (fluorouracil, carmustine, doxorubicin, cisplatin, taxotere, etc.), targeted therapy (e.g. as with HER2 targeting by trastuzumab) and radiotherapy.

Xenotransplantation studies have been a backbone of oncology research for four decades, and provide an effective research and evaluation environment for novel pharmaceutical compounds. Typically, these studies involve the implantation of tumorigenic human cell lines into immunocompromised mice, providing scientists with an in vivo model of tumor behavior in which to perform experiments including screening of novel cancer therapies, studies of cell behavior, and examination of metastasis. Patient-derived xenografts are a fundamental part of in vivo pharmacological research, aiding in the translation from benchtop to bedside.

Using xenograft models of gastric cancer is a powerful research tool, and there are many models of stomach cancer to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available, summarized in the table below. Models are often selected based on morphology, genetics, histology, early vs. late stage phenotype, invasive/aggressive properties, and abnormal protein expressions (usually relating to cell cycle, apoptosis, growth and angiogenesis). The goal of murine xenografts is to mirror human pathology and disease as closely as possible so that accurate insights into cellular events are achieved. This aspect is particularly critical with nonclinical drug testing for accurately evaluating compound efficacy.

Cell Line Characteristics
NCI-N87 ·    Adherent epithelial gastric carcinoma taken from a liver metastasis prior to cytotoxic therapy·    EGFR+, HER2+·    Oncogenes myc and erb B2 positive

·     Express carcinoembryonic antigen (CEA), TAG 72 surface glycoproteins, acetylcholine and muscarinic. They lack gastrin receptors and L-dopa decarboxylase.
SGC-7901 ·    Gastric carcinoma taken from a lymph node metastasis from a stage 4 patient·    Cytokeratin 20 and epithelial membrane antigen expression positive·    Demonstrates characteristics of mucous adenocarcinoma

·    When implanted in nude mice, frequent direct infiltration and lymphatic metastases are observed
HS746T ·    Epithelial/fibroblast cell type taken from a gastric carcinoma metastasis site in the left leg·    Vast variance in size, shape and staining with irregular nuclear shapes.·    Hypertriploid cells with complex karyotype
AGS ·    Epithelial gastric adenocarcinoma taken from tumor fragments of a patient with no prior cancer therapy·    Hyperdiploid cell line·    This cell line has been used to study obestatin/G protein-couple receptor 39 (GPR39), colon cancer associate transcript-1 (CCAT1) and Lactobacillus sps. behavior with gastric mucosa
MKN-45 ·    Poorly differentiated gastric adenocarcinoma derived from a liver metastasis·    Human hypertriploid karyotype·    In cell culture MKN-45 grow as spindle-shaped or oval cells

·    Wild-type p53, overexpresses c-met oncogene

·    Homozygous deletion of p16CDKN2/MTS1/INK4A and p15MTS2
SNU-16 ·    Poorly differentiated epithelial gastric carcinoma derived from metastatic ascites prior to chemotherapy·    Expresses carcinoembryonic antigen (CEA), TAG 72, fibroblast growth receptor 2 (FGR2), vasoactive intestinal peptide (VIP) and L-dopa decarboxylase (DDC) but lack gastrin receptors.·    Proto-oncogene c-myc is amplified

·    Hypotetraploid cell line
Cell Line Characteristics
SNU5 ·         Human epithelial gastric adenocarcinoma from metastatic ascites·         Isolated after chemotherapty with 5-fluorouracil, mitomycin-C and doxorubicin

·         Hypotetraploid karyotype

·         Multicellular aggregates in culture

·         Expresses carcinoembryonic antigen (CEA), L-dopa decarboxylase (DCC), TAG-72

·         Express receptors for acetylcholine, vasoactive intestinal peptide, muscarinic

·         Positive for oncogenes myc and erb B2

Gastric cancer is the fifth most common cancer worldwide, and it is often diagnosed at an advanced stage when it is more difficult to treat. Research in gastric cancer is focused on several key areas:

  1. Understanding the biology of gastric cancer: Researchers are working to understand the genetic and molecular mechanisms that drive the development and progression of gastric cancer. This includes identifying the genes and signaling pathways that are involved in tumor growth and metastasis, as well as the interactions between cancer cells and the surrounding microenvironment.
  2. Developing new treatments: There are several different types of treatments available for gastric cancer, including surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Researchers are working to develop new treatments that are more effective and have fewer side effects, such as combination therapies that target multiple pathways or drugs that activate the immune system to attack cancer cells.
  3. Improving screening and early detection: Early detection is key to successfully treating gastric cancer. Researchers are exploring new methods for screening and early detection, such as blood tests that detect cancer biomarkers, and developing technologies that can better detect and analyze early stage tumors.
  4. Identifying risk factors and prevention strategies: Researchers are studying the environmental, lifestyle, and genetic factors that contribute to the development of gastric cancer. This includes identifying modifiable risk factors such as diet and physical activity, as well as developing chemoprevention strategies that can reduce the risk of developing the disease.

Altogen Labs provides years of expert research in xenograft experiments taking advantage of the comprehensive expertise the company has developed in the use of in-house validated xenografts for gastric cancer research and clinical applications. Altogen Labs offers a complete suite of laboratory services, including:

  • xenotransplantation study design
  • selection of appropriate cancer model/cell line
  • host animal selection
  • subcutaneous or orthotopic xenografting
  • daily observation of experimental subjects
  • post-experiment analysis, including serum collection and histology

All laboratory studies are performed by experienced personnel in a GLP-compliant and IACUC-regulated facility in Austin, Texas. Please contact us at info@altogenlabs.com, or call 512-433-6177 to discuss xenograft study details.