Optimization of soft tissue sarcoma especially HT1080 cell line

Introduction: 

Sarcomas are rare tumours of the bones and soft tissues that affects all ages. Sarcomas contain special biological characteristics, that include a propensity for metastasis and a high incidence of aggressive local behaviour. Novel more efficacious therapies are slow to come to clinic in part because of the rarity of sarcoma that delays the progress of medical research. One type of sarcomas are soft tissue sarcomas (STS) that begins in the tissues that connect, support, and surround muscle, fat, blood vessels, nerves, tendons, and the lining of the patients’ joints. The most common occurs in the arms and legs, and in the abdomen. Some STS types are more likely to affect children, while others affect mostly adults. Diagnosis includes advanced imaging techniques, biopsy and surgical removal is the most common treatment, radiation and chemotherapy may be recommended-depending on the class of tumour. New novel therapies that are more tumour specific and less toxic are therefore required particularly for the treatment of paediatric sarcomas

Material and Methods: 

A panel of STSs were purchased from ATCC and optimised in clonogenic assay, spheroid regrowth delay and Chick embryo tumour models. Once optimised this assay cascade is now being utilised to assess the efficacy of novel combination therapies

Results and Discussions: 

Parameters were optimised for utilisation of STS cell lines in clonogenic assays. Due to the poor plating efficiency of STS cell lines large cell numbers had to be seeded to enable statistically relevant colony numbers to enable assessment of  single therapies in clonogenic survival assays. Furthermore, several methodologies were assessed for growth of these cell lines as multicellular tumour spheroids. STS cell lines did not form spheroids using the spinner flask method and optimal spheroid growth was achieved by utilisation of low attachment plates. The cells are currently being assessed for their ability to form tumours in Chick embryo tumour models to assess whether this model can be utilised for novel combination therapy development

Conclusion: 

Development of an assay cascade of 2D, 3D and nonmurine in vivo models will allow the assessment of novel combination therapies for STC. Once optimised the models will be utilised to assess the efficacy of combinations for STS, such as drugX and radiation.