Migration Stimulating Factor: New Marker for Tumour Progression?

Laface, Ilaria (2015). Migration Stimulating Factor: New Marker for Tumour Progression? PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000ef8f

Abstract

The aims of my work were: a) to generate reagents (recombinant protein and antibodies) useful to identify MSF as a possible marker for TAMs in human tumours; b) to characterise the biological properties of MSF. MSF is a soluble oncofoetal isoform of human fibronectin 1, identical to the N-terminus portion of fibronectin and characterized by the presence of a unique 10 amino acids long sequence in the C-terminus end. MSF is expressed by epithelial and stromal cells during foetal development and in cancer patients, but not by adult normal cells. Our group found a selective expression of MSF by M2-polarized human macrophages and M2-like tumor-associated macrophages (TAMs). TAMs are major inflammatory cells infiltrating tumors, they support tumour growth and are associated to poor prognosis. These findings suggest that MSF could be a potential marker for tumor progression associated to M2-like polarization of TAM and a promising target for anti-cancer therapy. Human MSF has been expressed in CHO cells and purified by affinity chromatography. Recombinant MSF has a motogenic effect on cancer cell lines, human monocytes and murine peritoneal macrophages. Different levels of MSF expression were observed in human cancer cell lines and correlate with its motogenic effect. In vivo experiments showed that tumors derived from MSF-expressing cells had an higher growth rate compared to tumors derived from control cells. We also developed a monoclonal antibody (MoAb_E10) recognizing human MSF. A initial characterization on human tumour tissues (lung, breast, colon) showed MSF expression in tumor cells as well as stromal cells. In particular MSF expression is associated to M2-like TAM. Given that TAMs are promising target for anticancer therapy, the possibility to identify M2 polarized cells would be of considerable interest and further studies will be necessary to define the importance of MSF in the context of human tumours.

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