HT1080 Xenograft Model
Sarcoma is a subtype of cancer that occurs in connective tissue cells (mesenchymal) that are transformed. Also known as sarcomatas, these cancers can affect cartilage, cancellous bone, blood, fat, vasculature and muscles. These cancers are relatively rare. The HT1080 cell line was established from a 35 YO male patient with fibrosarcoma who had not undergone previous therapy (radiotherapy or chemotherapy). The HT1080 model has been used in many biomedical research studies. Misra et al. (PLOSONE, 2012) used the HT1080 cell line for its ability to form aggressive angiogenic tumors in xenografted mice in order to study hypoxia-induced angiogenesis in tumors. Data showed that during hypoxia, HIF-1α mediates an upregulation of neuropilin-1 (NRP-1) that causes vasculogenic mimicry and tumor mimicry. Hanyu et al. (Cancer Science, 2009) used HT1080 xenografts to study imaging of angiogenesis in vivo. The group used a VEGF antibody to repress angiogenesis and found that the antibody also decreased lung metastasis using in vivo fluorescence to image tumor progression. Lastly, a 2010 Cancer Research article (Casal et al.) used HT1080 cells to study tumor plasticity with endothelial-like properties. Data showed the cells had the ability to form pseudovascular structures and identified the protease ADAMTS1 as critical for cells to display an endothelial-like gene signature. The HT1080 cell line is used to create the CDX (Cell Line Derived Xenograft) HT1080 xenograft mouse model. The HT1080 xenograft model has been used to study fibrosarcoma tumor biology (
Basic Study Design
- HT1080 cells are maintained in exponential growth phase under aseptic conditions.
- Cells are trypsinized and cell count viability is determined using a trypan blue exclusion assay (97-98% of cell viability is required). HT1080 cell suspension is adjusted to appropriate density.
- Each mouse is singly subcutaneously injected into the right flank with 106 cells in 100 µL of a Matrigel- HT1080 cell suspension.
- The injection sites are palpated up to three times weekly until tumors are established to an average size of 50-150 mm3 as measured via digital calipers.
- Animals are randomized into treatment groups. Administration of test compound is performed according to the pre-established treatment schedule.
- Mice weights are measured and recorded 3 times weekly; tumors are measured and recorded daily.
- End of study is reached when tumor size reaches 2,000 mm3 or the predetermined size limit per approved IACUC protocol.
- Final necropsy and tissue collections are performed for appropriate downstream analysis. Tumors are excised, weighed and documented by digital imaging. Tumors and tissues can be stabilized in RNAlater, snap frozen in LN2 or prepared for histology.