Role of CD70 in pathogenesis of ovarian cancer cell metastasis

 

American Journal of BioMedicine  Volume 2, Issue 11, pages1160-1174 November 2014


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

Abstract

American Cancer Society identifying ovarian carcinoma as the gynecologic malignancy with the highest case-to-fatality. Ovarian carcinoma metastasizes either by direct extension from the ovarian/fallopian tumor to neighboring organs (bladder/colon) or when cancer cells detach from the primary tumor. Exfoliated tumor cells are transported throughout the peritoneum by physiological peritoneal fluid and disseminate within the abdominal cavity. Extensive seeding of the peritoneal cavity by tumor cells is often associated with ascites, particularly in advanced, high-grade serous carcinomas. CD70 (encoded by the TNFSF7 gene) is a co-stimulatory factor present on B-cells, activated T-cells, and dendritic cells. CD70 is over expressed in tumor cells of various solid cancers including ovarian carcinoma, recently reported the role of  CD70 expression as a predictive marker of resistance to chemotherapy in ovarian cancers. We evaluated the expression of CD70 level in the pathogenesis of metastasis ovarian cancer cell. Seventy five tissue samples from metastatic ovarian carcinoma were evaluated by quantitative real-time PCR for CD70 and statistical analyses were performed using the Mann-Whitney test. Further, humanized anti-CD70 antibodies were investigated in xenograft mice models of ovarian cancer. Increasing expression of CD70 level was associated with increased risks for disease progression (HR = 1.04; 95% CI, 1.03 to 1.14) and death (HR = 1.13; 95% CI, 1.09 to 1.2). expression of CD70 was associated with a worse PFS and OS compared with non- expression of CD70 carcinomas. Furthermore, humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of ovarian cancer cell.

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


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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]

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