Abstract
Background: Plex-B1, the receptor of Sema4D, has been implicated in tumour growth, angiogenesis and metastasis. The binding of Sema4D to Plex-B1 can trigger the activation of Met tyrosine kinase, thereby promoting cell dissociation and invasive growth. We tested the hypothesis that the expression of Plex-B1, either alone or in association with Met, can be of predictive value for tumour progression.Methods: The expression and distribution of Plex-B1 and Met were investigated by immunohistochemistry and immunofluorescence in 50 human neoplasias originating in the breast and ovary, and correlated with clinical–pathological data at diagnosis.Results: Plex-B1 and Met were individually expressed in 14% and in 24% of the tumours, respectively. Plex-B1 and Met were co-expressed in 24/50 cases (48%), and in the majority of these (83%) Met was tyrosine phosphorylated. The expression of Plex-B1 or Met alone showed no significant correlation with tumour aggressiveness, whereas advanced stage tumours (III–IV) frequently showed Plex-B1–Met double-positive (9/13). Tumours co-expressing Plex-B1 and Met were characterised by worse grading and higher incidence of lymph node metastases. Out of 22 tumours with lymph node metastases, as many as 19 were Plex-B1 and Met double-positive (p=0.0008), and 17 expressed phosphorylated Met (p=0.002).Conclusions: Plex-B1 assumes a predictive value for unfavourable outcome when co-expressed with Met.
Highlights
Plexins constitute a family of widely expressed trans-membrane receptors for the semaphorins
Valente et al / Co-expression of plexin-B1 and Met in human breast and ovary tumours ogy with their ligands, as well as with Met and Ron, two cell surface tyrosine kinases belonging to the family of scatter factor receptors [1, 46]
We aimed at evaluating whether interactions between Plex-B1 and Met, both known to participate in the processes of cell migration/invasion, may associate with an increased risk of metastatic dissemination
Summary
Plexins constitute a family of widely expressed trans-membrane receptors for the semaphorins (see [42]). G. Valente et al / Co-expression of plexin-B1 and Met in human breast and ovary tumours ogy with their ligands (the semaphorins), as well as with Met and Ron, two cell surface tyrosine kinases belonging to the family of scatter factor receptors [1, 46]. The present study was designed to assess the potential value of Plex-B1 expression as a marker of tumour progression, either alone or in conjunction with that of the associated receptor Met. we aimed at evaluating whether interactions between Plex-B1 and Met, both known to participate in the processes of cell migration/invasion, may associate with an increased risk of metastatic dissemination. We tested the hypothesis that the expression of Plex-B1, either alone or in association with Met, can be of predictive value for tumour progression
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