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,  HCT-15

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)

Cell Line Characteristics
HCT15 ·         Human epithelial colon adenocarcinoma, tumorigenic·         Quasidiploid karyotype

·         Expresses carcinoembryonic antigen (CEA) and keratin

·         CSAp negative

·         Has been used to study nexrutine (NX), extracted from Phellodendron amurense

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

Colon cancer research is a broad field that encompasses many different areas of study, including the biology of colon cancer, the development of new treatments for the disease, and the identification of risk factors and strategies for prevention. Some of the key areas of research in colon cancer include:

  1. Understanding the biology of colon cancer: Researchers are working to understand the genetic and molecular mechanisms that drive the development and progression of colon 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 colon 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 colon cancer. Developing new methods for screening and early detection, such as blood tests that detect colon cancer biomarkers, and developing technologies that can better detect and analyze polyps and other precancerous lesions.
  4. Identifying risk factors and prevention strategies: Researchers are studying the environmental, lifestyle, and genetic factors that contribute to the development of colon 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 colon cancer disease.

Overall, colon cancer research is a critical area of study that has the potential to improve our understanding of the disease and develop new treatments and prevention strategies that can improve patient outcomes.