Role of CD70 in pathogenesis of ovarian cancer cell metastasis

Received January 14, 2020; Accepted April 27, 2020; Published May 21, 2020
http://dx.doi.org/10.18081/2333-5106/017-3/118-124


Jack L. Pincheira; Maria Wiseman; Florian K. Dinulescu

Abstract

This meta-analysis considers the previously published study that associated expression of CD70 by ovarian cancer cells with CD27-positive lymphocyte accumulation and poor patient prognosis. Here, a time-resolved approach to analysis has been used to give mechanistic insight and identify treatment stratagems from pre-existing data. For the bounded time period considered, CD70 expression was noted to cause a sequential increase in migration, colony formation, attachment, collagen invasion, and serous cavity invasion in the ovarian cancer cell line HEY, driven by NF-κB signaling leading to over-expressed Mucin-13, Y-box binding protein-1, and matrix metalloproteinase-9. Soluble CD27 had the opposite effect, by binding tumor cell CD70 and clearing activity of programmed death-ligand 1, while low-dose sorafenib downregulated expression of these same genes, through a multi-faceted effect on the NF-κB-JAK-STAT axis. The poor prognosis of CD70-positive ovarian cancer patients has garnered considerable current interest in CD70 as a cancer target, usually considered as something seen only in advanced disease. This is indeed the context in which we found ovarian cancer CD70 expression to drive a wide range of aggressive cell behaviors, focusing on the gain of function and sequential disease process from best to least. Data showing synergy of these negatively acting NF-κB-YY1-MMP-9 activities can be used to inform the treatment of future ovarian cancer patients over a bounded time period when EN2 is secreted and more precise multi-targeted therapy less plausible. The apparent selective advantage of gene-driven stepwise invasion capabilities and late stage B cell CD70 inhibition extend across many diseases and contributions to repertoire expansion.

Keywords: Ovarian cancer cell; CD70; Xenograft model; PCR


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