Pancreatic Cancer Xenograft

Altogen Labs validated Pancreatic Cancer Xenograft animal models:

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

Pancreatic cancer is a highly aggressive cancer that is often difficult to treat. Ongoing research is focused on improving our understanding of the biology of pancreatic cancer, developing new diagnostic approaches, and improving treatments for the pancreatic cancer.

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 xenograft models of pancreatic cancer is a powerful research application, 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 Line Characteristics
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 Line Characteristics
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

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.