Gastric Xenograft Model

Altogen Labs validated Gastric Cancer Xenograft animal models:

NCI-N87SGC-7901,  HS746T,  AGS,  MKN-45,  SNU-16

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.

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.

Using human xenograft models of gastric cancer, as previously mentioned, 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 xenografts and murine models 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 preclinical 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

Altogen Labs is one of the leading biology contract research organization (CRO) based in Austin, Texas. Altogen Labs provides years of expert research in xenograft experiments taking advantage of the comprehensive expertise the company has developed in the use of human tumor xenografts for research and clinical purposes. 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.