Colon Cancer Xenograft

Altogen Labs validated Colon Cancer Xenograft animal models:

COLO205,  CT-26,  MC38,  SW-620,  LS-174T,  WiDr,  SW480, HT-29,  RKO,  L0Vo,  HCT116,  DLD-1,  KM-12

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.

Colorectal cancer (CRC) describes malignant tissue of the colon, rectum or large intestine and most commonly affects those of older age. Symptoms often include bloody stools, weight loss, changes in bowel movements and chronic fatigue. Oftentimes CRC starts as a benign polyp that becomes cancerous. Polyps are relatively common in those over 50 years of age, which is why screening is recommended. Small polyps can be identified and removed while a tissue biopsy can be performed on larger polyps to determine whether they are malignant. Genetics (e.g. Gardner syndrome, familial adenomatous polyposis and Lynch syndrome), old age and inflammatory bowel disease are the most common risk factors for colon cancer. Malignant epithelial cells, or adenocarcinoma, are the most common type of colon cancer, although lymphoma and squamous cell carcinoma also exist. Immunohistochemistry and microscopy can be performed to look at cell structure, pluristratification, reduced stroma, mucus secretion, differentiation and CRC markers CK20 and MUC2. This can help with diagnosing characteristics and strategizing a treatment plan. The stage of epithelial-mesenchymal transition (EMT) is a critical indicator of cancer progression and it is thought that “tumor budding,” or individual cells at the invasive front of tumors, may be correlated this process. There are several common aberrant pathologies associated with CRC including the Wnt signaling pathway, the APC gene/protein, upregulated beta-catenin, the p53 gene/protein, TGF-beta, SMAD, KRAS, RAS, PI3K, and PTEN. Common treatment of CRC depends on the stage of the cancer and often includes some combination of surger (laparotomy or laparoscopic removal), chemotherapy (e.g. fluorouracil, oxaliplatin, capecitabine, UFT, irinotecan, bevacizumab, cetuximab, panitumumab), radiation (neoadjuvant or adjuvant) and immunotherapy.

Using human xenograft models of colorectal cancer, as previously mentioned, is a powerful research tool, and there are many models of colon cancer to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available. 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
COLO205 ·    Epithelial human colorectal adenocarcinoma

·    Expresses a 36kDa surface glycoprotein

·    Expresses keratin

·    Does not express colon specific antigen (CSAp)

CT-26 ·    Epithelial BALB/c mouse colon carcinoma induced by N-nitroso-N-methylurethane-(NNMU)

·    Aggressive phenotype with eliminated T-cell function

MC38 ·    Epithelial mouse colon adenocarcinoma

·    Overexpresses carcinoembryonic antigen (CEA)

·    Used to study insulin stimulated colon cancer proliferation

SW-620 ·    Human epithelial colorectal adenocarcinoma

·    Expresses transforming growth factor α, matrilysin, keratin and CEA

·    Do not express CSAp

·    Used for the study of late stage oncolytic virotherapy

LS-174T ·    Human epithelial colorectal adenocarcinoma

·    Positive for oncogene expression of N-myc, c-myc, H-ras, Myb, N-ras and fos

·    Displays abundant microvilli and vacuoles

·    Expresses CEA, interleukin 10 (IL-10), mucin and IL-6

WiDr ·    Epithelial human colon adenocarcinoma

·    Expresses carcinoembryonic antigen (CEA), transforming growth factor β, epidermal growth factor and colon-specific antigen (CSAp)

·    Overexpresses EGFR

SW480 ·    Epithelial human colorectal adenocarcinoma

·    Susceptible to human immunodeficiency virus 1

·    Expresses elevated p53 protein

·    Positive for oncogene expressions of c-myc, K-ras, N-ras, H-ras, sis, myb and fos

HT-29 ·    Epithelial human colorectal adenocarcinoma

·    Overexpresses mutated p53 and has deregulated c-myc oncogene

·    Expresses CEA and galactose ceramide

·    Sensitive to f-fluorouracil and oxaliplatin

·    Can induce differentiation and polarized morphology

·    Used to study transport, absorption and secretion of intestinal cells

L0Vo ·    Epithelial cell line from a metastatic tumor nodule fragment of colorectal adenocarcinoma in the left supraclavicular region

·    Well-differentiated with intestinal cell characteristics including microvilli, acinar structures, desmosomes, adherins, tight junctions and a glycoalyx.

·    Positive for expression of N-ras, H-ras, Myb, K-ras, c-myc, fos and sis oncogenes

HCT116 ·    Isolated from epithelial human tumorigenic colon growth

·    Spontaneous metastasis in mouse models

·    Mutated KRAS proto-oncogene

·    Used in tumor growth and apoptosis studies

DLD-1 ·    Epithelial adult male colorectal adenocarcinoma line

·    Does not express ros, src or abl oncogenes

·    Positive for myb, ras, myc, fos, p53 and sis oncogene expression

·    Expresses carcinoembryonic antigen (CEA), keratin, colon antigen 3 and a truncated adenomatous polyposis coli (APC) protein

KM-12 ·    Epithelial colorectal carcinoma (human)

·    Weakly metastatic

·    Used to study monotherapy efficacy (cetuximab, oxaliplatin) and combination studies to overcome oxaliplatin resistance (irinotecan)

RKO ·    Epithelial human colorectal carcinoma

·    Poorly differentiated

·    Wild type p53, h-TRbeta negative

·    Expresses urokinase receptor (u-PAR)

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 type T cells B cells NK cells Coat Other Notes
CD1 No Yes Yes White/albino Outbred
B6 Yes Yes Yes White/albino Inbred
Balb/c No Yes Yes Nude, albino Inbred
Balb/SCID No No Yes White Inbred
NOD/SCID No No Impaired White Inbred
Nu/nu No Yes Yes Nude Outbred
CD57BL Yes Yes Yes Dark brown/black Inbred
CB17 Yes Yes Yes White Inbred
NSG No No No White Inbred
Swiss Nude No Yes Yes Nude Outbred

 

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.