HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells | Journal of Ovarian Research | Full Text

Full Text (technical)
  Published: 17 May 2016

....Human epididymis protein-4 (HE4/WFDC2) is a small secretory protein that belongs to the family of whey acidic protein (WAP) domain-containing anti-proteases [3], and has been shown to possess cross-class anti-protease activity itself [4]. It is overexpressed in ovarian cancer tissues compared to normal ovaries, and has been identified as a novel biomarker for EOC [5, 6]. Serum levels predict ovarian cancer with equivalent sensitivity to CA125, but with the advantage that HE4 is less frequently elevated in patients with benign gynecological conditions [5]. A multicenter study led by our institution established a new algorithm for the diagnosis of women with an ovarian mass [6]. The FDA-approved Risk of Ovarian Malignancy Algorithm (ROMA) uses HE4 along with CA125 and menopausal status to predict a woman’s risk of ovarian cancer and monitor disease with improved sensitivity and specificity over the Risk of Malignancy Index (RMI) that used CA125, pelvic sonography, and menopausal status [6].

Recently, HE4 has been associated with the development of chemoresistance clinically.....

Discussion

The ways in which HE4 affects chemoresistance are likely multi-factorial and cell type-specific. In cells that already display a high degree of chemoresistance due to other mechanisms, such as OVCAR8 cells, the effect of increasing levels of HE4 may be minimal. In contrast, in cells with low levels of HE4 that are not as chemoresistant, increasing the level of HE4 may produce dramatic changes in apoptotic response to drug treatment, as we have observed in SKOV3 cells....

 
(abstract) Conclusion:

Overexpression of HE4 promotes collateral resistance to cisplatin and paclitaxel, and downregulation of HE4 partially reverses this chemoresistance. Multiple factors could be involved in HE4-mediated chemoresistance, including deregulation of MAPK signaling, as well as alterations in tubulin levels or stability.