HCC1954 Xenograft Model

HCC1954 Xenograft Model

The ACS approximates for 2019, United States breast cancer rates are: Around 268,600 new invasive breast cancer cases, 62,930 new cases of breast cancer in situ (CIS, meaning non-invasive or early stage) and 41,760 fatalities attributed to breast carcinoma. Recently data shows the past few years have demonstrated a small increase in the rates of breast cancer (+0.4%/year). The HCC1954 cell line was derived from the stage II breast cancer of a 61yo East Indian female diagnosed with ductal carcinoma.

The HCC1954 model has been used in many breast cancer research studies. Beyer et al. (Cancer Research, 2011) used the HCC1954 model to study how to improve the efficacy of monoclonal antibody therapy in breast cancer using JO-1 (Junction opener 1), a small recombinant adenovirus protein derived from serotype 3. Results showed JO-1 binds to DSG2 and combination of JO-1 with Erbitux (cetiximab) or trastuzumab (Herceptin) increased therapeutic efficacy in part due to improved target access. In 2016, Xiong et al. published an Oncotarget study using HCC1954 cells to study CD147 knockdown in improving trastuzumab, a HER2 antibody, efficacy treatment in breast cancer. Results demonstrated that suppressing CD147 (knockdown) with trastuzumab treatment resulted in increased apoptosis (Caspase-3 cleaving and PARP marker) and decreased MAPK and Akt phosphorylation. This data has implications for trastuzumab antibody drug resistance/sensitivity for treating breast cancer. Finally, He et al. published a 2017 Science Reports study using HCC1954 to evaluate androgen receptor targeting in HER2 expressing brast cancer. Results demonstrated using Enzalutamide, an anti-androgen agent, with trastuzumab successfully decreased cancer growth and Ki67 staining. The HCC1954 cell line is used to create the CDX (Cell Line Derived Xenograft) HCC1954 xenograft mouse model. The HCC1954 xenograft model has been used to investigate breast carcinoma treatments and therapies (cetuximab, JO-1, trastuzumab, etc.).

Basic Study Design

  1. HCC1954 cells are maintained in exponential growth phase under aseptic conditions.
  2. Cells are trypsinized and cell count viability is determined using a trypan blue exclusion assay (98% of cell viability is required).  HCC1954 cell suspension is adjusted to appropriate density.
  3. Each mouse is singly subcutaneously injected into the right flank with 106 cells in 100 µL of a Matrigel – HCC1954 cell suspension.
  4. The injection sites are palpated up to three times weekly until tumors are established to an average size of 50-100 mm3 as measured via digital calipers.
  5. Animals are randomized into treatment groups. Administration of test compound is performed according to the preestablished treatment schedule.
  6. Mice weights are measured and recorded 3 times weekly; tumors are measured and recorded daily.
  7. End of study is reached when tumor size reaches 2,000 mmor the predetermined size limit per approved IACUC protocol.
  8. 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.