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
References
1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun M. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249. [PubMed]
2. Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20:1248–1259. [PubMed]
3. Naora H. Developmental patterning in the wrong context: the paradox of epithelial ovarian cancer. Cell Cycle. 2005;4:1033–1035. [PubMed]
4. Grewal IS. CD70 as a therapeutic target in human malignancies. Expert Opin Ther Targets 2008;12(3):341-51.[PubMed]
5. Kurman R, Visvanathan K, Roden R, Wu TC, Shih I-M. Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis. Am J Obstet Gynecol. 2008:351–356. [PubMed]
6. Liu N, Sheng X, Liu Y, Zhang X, Yu J. Increased CD70 expression is associated with clinical resistance to cisplatin-based chemotherapy and poor survival in advanced ovarian carcinomas. OncoTargets Ther. 2013;6:615-619.
7. Powell B, Kenley E, Chen LM, Crawford B, McLennan J, Zaloudek C, Komaromy M, Beattie M, Ziegler J. Risk-reducing salpingo-ophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol 2005;23:127–132. [PubMed]
8. Oflazoglu E, Stone IJ, Gordon K, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(19):6171-6180.
9. Folkins AK, Jarboe EA, Roh MH, Crum CP. Precursor to pelvic serous carcinoma and their clinical implications. Gynecol Oncol 2009;113:391–396. [PubMed]
10. Douin-Echinard V, Péron J-M, Lauwers-Cancès V, Favre G, Couderc B. Involvement of CD70 and CD80 intracytoplasmic domains in the co-stimulatory signal required to provide an antitumor immune response. Int Immunol. 2003;15(3):359-372.
11. Auersperg N, Woo MMM, Gilks CB. The origin of ovarian carcinomas: a developmental view. Gynecol Oncol 2008;110:452–454. [PubMed]
12. Aulwurm S, Wischhusen J, Friese M, Borst J, Weller M. Immune stimulatory effects of CD70 override CD70-mediated immune cell apoptosis in rodent glioma models and confer long-lasting antiglioma immunity in vivo. Int J Cancer J Int Cancer.2006;118(7):1728-1735.
13. Shih I-M, Kurman R. Ovarian tumorigenesis: a proposed model based on morpholgical and molecular genetic analysis. Am J Pathol 2004;164:1511–1518. [PubMed]
14. Grewal IS. CD70 as a therapeutic target in human malignancies. Expert Opin Ther Targets.2008;12(3):341-351
15. Yousif NG. Fibronectin promotes migration and invasion of ovarian cancer cells through up-regulation of FAK-PI3K/Akt pathway. Cell Biol Int 2014;38(1):85-91.[PubMed]
16. Jilaveanu LB, Sznol J, Aziz SA, Duchen D, Kluger HM, Camp RL. CD70 expression patterns in renal cell carcinoma. Hum Pathol. 2012;43(9):1394-1399.
17. Hsu C-Y, Bristow RE, Cha MS, Wang B, Ho CL, Kurman R, Wang TL, Shih I-M. Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas. Clin Cancer Res 2004;10:6432–6436. [PubMed]
18. Haverty PM, Hon LS, Kaminker JS, Chant J, Zhang Z. High resolution analysis of copy number alterations and associated expression changes in ovarian tumors. BMC Med Genomics 2009;2:21. [PubMed]
19. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA: a cancer journal for clinicians 2006; 56(2):106-130. [PubMed]
20. Gorringe KL, Jacobs S, Thompson ER, Sridhar A, Qiu W, Choong DY, Campbell IG. High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications. Clin Cancer Res 2007; 13(16):4731-4739. [PubMed]
21. Jacobs S, Thompson ER, Nannya Y, et al. Genome-wide, high-resolution detection of copy number, loss of heterozygosity, and genotypes from formalin-fixed, paraffin-embedded tumor tissue using microarrays. Cancer Res 2007;67:2544–51. [Abstarct/Full-Text]
