Fibronectin (FN) is a key component of the extracellular matrix (ECM) which can be degraded to form bioactive fragments having distinct activities. Tumour cells expressing high levels of proteases and altered patterns of ECM receptors (integrins) may interact differently with the ECM than normal cells.

Objectives: To investigate the effect of FN and its 120 kDa fragment on epithelial cell motility and matrix metalloproteinase (MMP) secretion.

Methods: Oral squamous cell carcinoma cell lines expressing high (VB6) and low (C1) levels of the b6 integrin were used along with normal keratinocytes (NHK). Migration of all cell lines was measured using transwellŽ plates coated with FN or 120kDa FN fragment. MMP-2 and 9 secretion was measured by gelatin zymography following plating of the cells on intact pFN and 120kDa FN fragment. Expression of the b6 integrin was assessed by flow cytometry. Staining for cellular FN (cFN), MMP-9 and b6 integrin in cancer resections was carried out using immunohistochemistry.

Results: Migration on the 120kDa FN fragment was one and a half to two fold higher than on the intact molecule in b6 expressing cells but not in the C1 or NHK. This increase in motility was not achieved by changes in cell adhesion. MMP-9 and MMP-2 were upregulated when VB6 cells were plated on the 120kDa FN fragment. Staining of cFN was observed around the invading front of cancer sections.

Conclusion: The 120kDa FN fragment upregulates and cell motility specifically in cells expressing high levels of b6 integrin and may achieve this by upregulation of MMP-2 and 9. We speculate that in tumours, MMPs may degrade FN to form fragments around lesions which increase cell motility and further MMP production in a positive feed-back loop. This fragment being indicative of a number of pro-tumourigenic processes may be of use as a prognostic marker.

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