Ovarian Cancer Xenograft

Altogen Labs validated Ovarian Cancer Xenograft animal models:

OV-CAR3,  SKOV-3

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.

Ovarian cancer can form either in or on an ovary that can metastasize to other organs. Early stage symptoms are unclear and later stage symptoms include loss of appetite, abdominal swelling, changes in menstrual cycle, bloating and pelvic pain. The most common organs for ovarian cancer metastasis include lymph nodes, liver, lungs and abdomen lining. Ovarian cancer is correlated to the amount of time spent ovulating as this is a process of increased cell growth and proliferation to repair the corpus luteum from the egg follicle burst required to release an egg. Risk factors include post-menopausal hormone therapy, fertility treatments, inherited genetics (including BRCA1 and BRCA2 mutations and Lynch syndrome), hormonal conditions (polycystic ovarian syndrome, endometriosis), obesity and never having children. On the other hand certain factors that can decrease risk include breast feeding, hormonal birth control, hysterectomy and tubal ligation. Dysregulated genes associated with the development of ovarian cancer include Her2/neu, NF1, CDK12, PTEN, p53, ERBB2, PIK3CA, KRAS, BRAF, ARID1A, BRIP1, RAD51C, MSH6, RAD51D, CHD1, CHECK2, RAD50 and PALB2. Ovarian cancer has several subtypes based on which cell type is affected. Ovarian carcinoma accounts for over 90% of ovarian cancer cases and affect epithelial ovarian tissue. Some rarer carcinomas can develop from groups of epithelial ovarian cells in the stroma called cortical inclusion cysts. High-grade serous carcinoma is the most common ovarian carcinoma and is a Type II (aggressive) cancer type with genomic instability of a high degree. Serous carcinomas are thought to develop from tubal intraepithelial tissue (of the Fallopian tubes) rather than ovarian tissue and are characterized by anaplasia, nuclear atypia and the presence of psammoma bodies. On the other hand, Type 1 cancers are associated with microsatellite instability in some of the genes listed above and are generally much less aggressive. Other subtypes of ovarian carcinoma can develop from germ cells or sex cord stromal cells (Peutz-Jeghers syndrome has been associated with the development of this subtype). Diagnosis of ovarian cancers include blood tests (screening for CA-125, CA-19-9, CA15-3, OVX1, immunosuppressive acidic protein, haptoglobin-α, mesothelin, osteopontin, lysophosphatidic acid, fibroblast growth factor 23), serum evaluation (alpha-fetoprotein, neuron-specific enolase, lactate dehydrogenase), pelvic exams, transvaginal ultrasounds, or rectovaginal examinations. Biopsies and histopathologic evaluations are used to further characterize or confirm cell or tumor type as there are dozens of ovarian cancer subtypes. Treatment options include surgery (uni or bi-lateral omentectomy, hysterectomy, saphingectomy, lymphadenectomy), debulking (surgical resection of metastases to improve survival for advanced cancers), chemotherapy (bevacizumab, platinum-based drugs, paclitaxel, docetaxel, bleomycin, etoposide, PARP inhibitors, etc.), radiotherapy (which can result in infertility), hormonal therapy (targeting estrogen receptors), and immunotherapy. Ovarian cancers have a poor prognosis due to the difficulty in catching early-stage cancers; many women are diagnosed at stage III or IV.

Using human xenograft models of ovarian cancer, as previously mentioned, is a powerful research tool, and there are several models of ovarian 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
OV-CAR3 ·    Human epithelial line derived from malignant ascites of a high grade ovarian adenocarcinoma

·    Isolated after patient had combination therapy with Adriamycin, cyclophosphamide and cisplatin.

·    Abnormal aneuploid karyotype

·    Androgen receptor, estrogen receptor and progesterone receptor positive

·    Resistant to Adriamycin, melphalan and cisplatin at clinically relevant concentrations

·    Xenografts and cell line are histologically similar to original patient tumor

·    Used for drug resistance studies as well as hormonal therapy studies

SKOV-3 ·    Human epithelial line from a primary ovarian cystadenocarcinoma

·    Resistant to tumor necrosis

·    Resistant to cytotoxic drugs such as cisplatinum, Adriamycin and dipthera toxin

·    Hypodiploid karyotype

·    Overexpresses the integrin-associated protein (IAP) CD47

·    Vimentin (VM), low molecular weight cytokeratin (LMWK), high molecular weight cytokeratin (HMWK), leucocyte common antigen (LCA) and epithelial membrane antigen (EMA) 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 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.