Loss of expression of bone morphogenetic protein-10 (BMP-10) in ovarian cancer cells appears to be a marker for poor prognosis, investigators claim.
Low expression of BMP-10 in ovarian cancer tissues and cell lines significantly correlated with higher-stage disease, high-risk features, and poor prognosis. Conversely, over-expression of BMP-10 was significantly associated with inhibition of ovarian cancer cell proliferation, migration, and invasion, reported Yufeng Jin, PhD, and colleagues from Nantong (China) University.
“Loss of BMP-10 expression might represent a poor prognosis in ovarian cancer patients. Meanwhile, loss of BMP-10 could promote malignant behaviors in ovarian cell lines, suggesting it might be a promising tumor suppressor,” they wrote in Pathology – Research and Practice.
Other members of the BMP family of cytokines and metabolites have recently been implicated in development of esophageal squamous cell cancer, breast cancer, and colorectal cancer, and BMP-10 has been linked to ovarian tumor progression, the investigators noted.
To get a better sense of BMP-10’s potential role as an ovarian cancer suppressor, the investigators first examined eight paired samples of ovarian cancers and adjacent normal tissues, and observed that in most pairs expression of the protein was significantly lower in the cancerous tissues (P less than .01).
Next, they looked at BMP-10 expression in ovarian tissues with varying histological grades; they found that it was overexpressed in normal tissues, but underexpressed in ovarian cancer tissues, especially those from patients with advanced grade disease.
The investigators then looked at the association between BMP-10 expression and clinicopathologic features, using a cutoff of 30% as a mean value for BMP-10 expression in tissues. They found the expression of the protein trended toward correlation with FIGO (International Federation of Gynecology and Obstetrics) stage (P = .08) and correlated significantly with histologic grade (P = .018), lymph node metastasis (P = .004), and peritoneal fluid (P = .032). There were no significant correlations with patient age, histologic subtype, residual tumor size or tumor cells in peritoneal fluid, however.
The authors also found that patients whose tissues had low levels of BMP-10 expression had significantly shorter overall survival (P less than .01), and in multivariate analysis, they saw that expression of the protein was an independent prognostic factor (hazard ratio, 4.834; P = .002).
Turning to in vitro studies, they observed that overexpression of the protein inhibited proliferation of an ovarian cancer cell line (Ovca3), while introduction of an antibody that neutralized BMP-10 allowed proliferation to occur unimpeded.
Finally, they showed that BMP-10 overexpression impaired the wound-healing and invasive properties of Ovca3 cells, while knockdown of the protein’s expression promoted migration and invasion of a different ovarian carcinoma cell line (Skov3).
The investigators acknowledged that their study was limited by small sample sizes, and they noted that they did not investigate potential mechanisms for BMP-10’s effect on ovarian cells.
Nonetheless, they concluded that “BMP-10 should be considered as a promising prognostic marker and a crucial regulator for progression of ovarian cancer.”
The study was supported by the Nantong Health and Family Planning Commission. All authors declared having no conflicts of interest.
SOURCE: Jin Y et al. Pathol Res Pract. 2019 Oct 28. doi: 10.1016/j.prp.2018.10.025.