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’Follow my leader’: in vitro studies of oral cancer cell motility


Project Description

Oral cancer cell invasion is a crucial step in the progression of the disease and is mediated by interactions with the extra cellular matrix and factors released by the tumour cells as well as cells that occupy the tumour microenvironment (stroma). Pilot studies in our laboratories have shown that factors released into the culture medium (conditioned medium, CM) from more invasive oral squamous cell carcinoma cell lines (H376) can enhance the invasion of less motile cells (H357) but the mechanism by which this occurs is unclear. What is clearer is the role of fibroblasts in the stroma surrounding the tumour, the presence of which is known to enhance tumour cell invasion and features of which may be of more use diagnostically than those of the tumour itself (1).

We hypothese that i) invasive tumour cells stimulate the migration of less invasive cells and ii) that the phenotype of fibroblasts determines the influence that such cells have on tumour cell motility.

Specific objectives include:
1. Examination of H357 and H376 migration towards collagen I and fibronectin in 2D cultures and invasion of collagen I gels in 3D cultures (2).
2. Treatment of one cancer cell line with the conditioned medium of the other to observe any effects on migration and invasion.
3. Investigate the role of extra cellular vesicles in this communication by centrifuging the CM to eliminate these and compare results to non-centrifuged samples.
4. Examine the effect on tumour cell migration and invasion of CM from normal oral fibroblasts and cancer-associated fibroblasts.
Training will be given in cell culture maintenance and cell motility assays including the preparation of 3D models, many of which are routinely used by members of the laboratory. This project will shed further light on the complex interactions which occur as part of the invasive process in oral cancer.

Funding Notes

This project is open to self-funded or sponsored applicants. Candidates must have a first or upper second class honors degree or significant research experience.

References

1. Marsh D et al. Stromal features are predictive of disease mortality in oral cancer patients. J Pathol. 2011; 223: 470-81
2. Moharamzadeh K et al Tissue engineered oral mucosa. J Dent Res. 2012; 91: 642-50

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