DMS273 Xenograft Model

DMS273 Xenograft Model

There are over 234,000 new lung cancer cases diagnosed yearly in the United States with over 154,000 annual deaths attributed to the disease. Lung cancer is mostly diagnosed in patients over 65 years of age, with the risk being much higher for those who are smokers. Non-small cell lung cancer (NSCLC) and small cell lung cancer are the primary types. Small-cell carcinoma of the lung is highly malignant and generally displays faster doubling times and metastasis development. The DMS273 cell line was first established in 1978 by Dr. G D Sorenson of the Lebanon Dartmouth Medical School from the pleural effusion of a previously-treated 50YO Caucasian female patient with small cell lung cancer. DMS273 cells have since been used in many liver cancer studies. In 1997, Yamori et al. (Japanese Journal of Cancer Research) used various lung cancer lines, including DMS273, to examine the efficacy of proposed anti-tumor drug paclitaxel. Today, paclitaxel is a well-known lung, breast, Kaposi sarcoma and lung chemotherapy treatment. In a Cancer Science study, Shuichi et al. (2015) used the DMS273 model to establish a GFP-labeled subline and generated a xenograft via orthotopic transplantation in order to observe metastasis patterns of this small-cell lung cancer model. Using this technique, the group isolated a bone metastasis subline termed G3H and indicated that hepatocyte growth factor and MET signaling pathways greatly contributed to invasion activities. Finally, in a 2006 Nature article, Masuda et al. used the DMS-273 xenograft model in examining the antitumor efficacy of kigamicin D, an agent which targets the ability of cancer cells to tolerate nutrient deprivation. Results demonstrated that while kigamicin D was effective against pancreatic xenografts, it only showed weakly antitumor effects in other models such as DMS-273 and murine syngeneic tumors while in IMC-carcinoma tumor growth actually increased. This data suggests a possible beneficial immune response and highlights the importance of testing agents against a spectrum of cancer types. The DMS273 cell line is used to create the CDX (Cell Line Derived Xenograft) DMS273 xenograft mouse model. The DMS273 xenograft model has been used as a model for studying novel therapies and combination treatments in the highly metastatic small-cell lung cancers.

Basic Study Design

  1. DMS273 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).  DMS273 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- DMS273 cell suspension.
  4. 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.
  5. Animals are randomized into treatment groups. Administration of test compound is performed according to the pre-established 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.