Pancreatic Cancer Xenograft

Altogen Labs validated Pancreatic Cancer Xenograft animal models:

AsPC-1,  Capan-1,  MIAPaCa-2,  BxPc-3,  PANC-1

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.

Pancreatic cancer most commonly affects people over 40 years of age. Symptoms include abdominal or back pain, yellow skin (Jaundice), weight loss, loss of appetite and dark urine. Risk factors include smoking, diabetes, obesity and genetics; factors that lower risk include healthy weight, low red meat in the diet and not smoking. The two primary types of pancreatic cancer occur in either the exocrine cells or the endocrine cells. Exocrine cancer are also referred to as invasive or ductal carcinoma. Most exocrine adenocarcinomas start in the head of the pancreas in ducts that carry enzymes, bicarbonate and other secretions. It is rarer for cancer to originate in the cells which produce digestive enzymes, which is called acinar cell carcinoma. Rarer still are cystadenocarcinoma, pancreatoblastoma (mostly a childhood cancer), adenosquamous carcinoma, hepatoid carcinoma, signet ring cell carcinoma, colloid carcinoma, undifferentiated carcinoma (including those with osteoclast-like giant cells) and solid pseudopapillary tumors. Cancers that occur in the endocrine cells are known as neuroendocrine tumors (NETs). They are hormone-producing cells that are responsible for bridging the endocrine and nervous systems. Common hormones secreted include insulin, glucagon and gastrin, and the subtypes of NETs are named after these hormones such as insulinomas and gastrinomas. Genes that contribute to invasive properties when mutated include KRAS, CDKN2A, TP53, SWI-SNF,  DAXX, mTOR, ATRX and SMAD4. Diagnosis of pancreatic cancer is typically through medical imaging including CT scans, MRI, positron emission tomography (PET) and endoscopic or abdominal ultrasounds, and blood tests and biopsies can further evaluate the specific cell types involved. CA19-9 is a tumor marker associated in pancreatic cancer but is not universally elevated and therefore is not completely reliable. Staging follows TNM classification; tumor size (T), spread to lymph nodes (N) and metastasis (M). Early detection is key to improving prognosis; 5-year survival rate rises from 5% to 20% when diagnosed in early rather than late stages. Treatment includes resection (depending on feasibility), neoadjuvant therapy, chemotherapy and radiotherapy. The Whipple procedure refers creating a bypass for food from the stomach directly to the jejunum, making removal of pancreatic head and duodenum feasible. Chemotherapies include gemcitabine, 5-fluorouracil, erlotinib, protein-bound paclitaxel, somatostatin analogs, everolimus or sunitinib.

Using human xenograft models of pancreatic cancer, as previously mentioned, is a powerful research tool, and there are several models of pancreatic 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 LineCharacteristics
AsPC-1·    Epithelial human tissue from metastatic ascites of pancreatic adenocarcinoma·    Expresses carcinoembryonic antigen (CEA), mucin, human pancreas specific antigen and human pancreas associated antigen

·    Used for study pancreas infections

Mia PaCa-2·    Human epithelial pancreatic ductal adenocarcinoma·    Hyoptriploid karyotype

·    Attached epithelial and floating round morphology

·    Expresses CK5.6, E-cadherin, AE1/AE3, vimentin, synaptophysin, chromogranin A, NTR1, human colony stimulating factor I, plasminogen activator and SSR2

·    Lacks CD56

BxPC3·    Epithelial human pancreatic adenocarcinoma·    Epithelial morphology with moderate differentiation

·    Wild type KRAS

·    Overexpresses cancer stem cell markers, IL-8, PGE2 and VEGF

·    Expresses mucin, CEA and pancreas cancer specific antigen

PANC-1·    Poorly differentiated epithelial human cell line from pancreatic ductal adenocarcinoma·    Expresses chondroitin sulfate E (CS-E)

·    Hypertriploid karyotype

Cell LineCharacteristics
Capan-1●        Human epithelial pancreatic cancer line

●        Hypotriploid karyotype

●        Expresses mucin, cystic fibrosis transmembrane conductance regulator, HLA A1, A9, B17 and B13

●        Progesterone and estrogen receptor positive

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

Mouse strains available at Altogen Labs:

Mouse typeT cellsB cellsNK cellsCoatOther Notes
CD1NoYesYesWhite/albinoOutbred
B6YesYesYesWhite/albinoInbred
Balb/cNoYesYesNude, albinoInbred
Balb/SCIDNoNoYesWhiteInbred
NOD/SCIDNoNoImpairedWhiteInbred
Nu/nuNoYesYesNudeOutbred
CD57BLYesYesYesDark brown/blackInbred
CB17YesYesYesWhiteInbred
NSGNoNoNoWhiteInbred
Swiss NudeNoYesYesNudeOutbred

About the models

CD1

This model originates from a non-inbred Swiss stock of the 1920s from the Centre Anticancerux Romand (Lausanne, Switzerland). Outbred stocks are generally used for their genetic variability.

B6

This strain of mouse arose from a spontaneous mutation in the C57BL/6 strain resulting in a coisogenic albino mutant. These mice have a mutant tyrosinase gene.

Balb/c

This strain of nude mouse was developed in the 1980s through many crosses and backcrosses and remains to be an inbred model. Balb/c mice do not have a thymus and therefore cannot produce T-cells and are considered immunodeficient. Balb/c mice are often used for their easy breeding and similar weights (low-variation) of males and females. They are also used for monoclonal antibody production.

Balb/SCID

This mouse model lacks functioning T and B cells but do have functioning NK cells which limits engraftment. These mice are sensitive to irradiation and have functioning macrophages, dendritic cells and complement activity. Some cancer cell lines show improved engraftment over nude models in Balb/SCID mice.

NOD/SCID

The homozygous SCID mutation results in impaired T cell and B cell lymphocyte development. The NOD characteristic results in impaired natural killer cell function. NOD/SCID mice also lack macrophage and dendritic cell activity as well as reduced complement activity. These mice have a non-obese diabetic and insulitis background and low cytokine production. NOD/SCID mice exhibit a 36-week median survival due to the development of thymic lymphomas, which limits their use to short-term experiments.

Nu/nu

These mice originate from the National Institute of Health (NIH). Originally thought to be BALB/C congenic mice, once it was discovered that these mice were outbred they were determined to be of their own strain. These mice do not have a thymus, or T-cells, and are nude immunodeficient models.

CD57BL/6

This laboratory mouse strain was the 2nd mammalian species to ever have its genome published in entirety. They originate from the Bussey Institute for Research in Applied Biology in 1921. These mice are often selected for easy breeding and availability of congenic strains. These mice are particularly sensitive to odors, noise, pain, cold, alcohol and morphine addiction.

CB17

CB17 mice are of a congenic strain that carry the immunoglobulin heavy chain allele (Igh-1b) from a C57BL/Ka on a BALB/c background. They are an ideal control for the CB17/SCID immunodeficient mouse model

NSG

Also known as NOD scid gamma, these mice are deficient in NK, T and B cells as well as multiple cytokine pathways. They also have reduced dendritic cell function and defective macrophage activity and lack a complement system. They are one of the most immunodeficient models available and unlike NOD/SCID mice, NSG mice do not develop thymic lymphomas and can be used for long-term experiments.

Swiss Nude

These mice originate from the 1974 Gustave Roussy Institute (Villejuif, France) Swiss stock. They are T cell deficient, nude and albino.

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.