The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling.
Bottom Line: NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness.This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR).Our results point to NCAM-mediated stimulation of FGFR as a novel mechanism underlying EOC malignancy and indicate that this interplay may represent a valuable therapeutic target.
Affiliation: IFOM - The FIRC Institute of Molecular Oncology, Milano, Italy.Show MeSH
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Mentions: We therefore asked if this interaction could be specifically targeted to interfere with tumour dissemination. To address this question, mice xenotransplanted with SKOV3-NCAM cells were subjected to i.p. treatment with the mAb 123C3 that, as described above, interferes with NCAM-mediated activation of FGFR. The dissemination of SKOV3-NCAM cells to bowel and diaphragm was dramatically reduced in 123C3-treated mice, and a significant decrease was also observed in liver metastasis. In contrast, a control mAb showed no effect in SKOV3 cell dissemination (Fig 7). The mAb 123C3 does not cross-react with mouse NCAM (not shown), thus its inhibitory function on EOC metastasis is due to the neutralization of NCAM in cancer cells rather than in the microenvironment. These findings indicate that antibody-mediated targeting of the NCAM/FGFR interplay suppresses the metastatic potential of EOC cells, an observation that has relevant therapeutic implications.
Affiliation: IFOM - The FIRC Institute of Molecular Oncology, Milano, Italy.