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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Polyploid giant cancer cells with budding and the expression of cyclin E, S-phase kinase-associated protein 2, stathmin associated with the grading and metastasis in serous ovarian tumor

Authors: Hongcheng Lv, Yang Shi, Li Zhang, Dan Zhang, Guang Liu, Zhengduo Yang, Yan Li, Fei Fei, Shiwu Zhang

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and express cell cycle-related proteins. HEY PGCCs induced by cobalt chloride generated daughter cells and the daughter cells had a strong migratory and invasive ability. This study is to compare the expression of cyclin E, S-phase kinase-associated protein 2 (SKP2), and stathmin between PGCCs with budding and control HEY cells, and determine the clinicopathological significance of cell cycle-related protein expression in ovarian tumors.

Methods

We used western blot and immunocytochemical staining to compare the expression levels of cyclin E, SKP2 and stathmin between PGCC with budding daughter cells and control HEY cells. In addition, immunohistochemical staining for cyclin E, SKP2 and stathmin was performed on a total of 80 paraffin-embedded serous ovarian tumor tissue samples. The samples included 21 cases of primary high-grade carcinoma (group I) and their metastatic tumors (group II), 26 cases of primary low-grade carcinoma without metastasis (group III), and 12 cases of serous borderline cystadenoma (group IV).

Results

Single PGCC with budding in the stroma showed high correlation with the metastasis of ovarian carcinoma. Group I had a significantly higher number of single PGCCs with budding in the stroma than group III (85.71% [18/21] vs. 23.08% [6/26] cases; χ 2 = 18.240, P = 0.000). The expression of cyclin E, SKP2, and stathmin was compared among the four groups. The expression levels of cyclin E, SKP2, and stathmin increased with the malignant grade of ovarian tumors and group II had the highest expression levels. The expression of cyclin E (χ 2 = 17.985, P = 0.000), SKP2 (χ 2 = 12.384, P = 0.000), and stathmin (χ 2 = 20.226, P = 0.000) was significantly different among the 4 groups.

Conclusions

These data suggest that the cell cycle-related proteins cyclin E, SKP2, and stathmin may be valuable biomarkers to evaluate the metastasis in patients with ovarian serous carcinoma.
Appendix
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Literature
1.
Rauh-Hain JA, Diver EJ, Clemmer JT, Bradford LS, Clark RM, Growdon WB, Goodman AK, Boruta DM, Schorge JO, del Carmen MG: Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: a SEER analysis. Gynecol Oncol. 2013, 131 (1): 46-51.CrossRefPubMed
2.
Yin M, Li C, Li X, Lou G, Miao B, Liu X, Meng F, Zhang H, Chen X, Sun M, Ling Q, Zhou R: Over-expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer. J Surg Oncol. 2011, 104 (1): 29-36.CrossRefPubMed
3.
Palmer J, Jivraj S, Galimberti A, Paterson M: Serous ovarian carcinoma in pregnancy. BMJ Case Rep. 2009, 2009-bcr04.2009.1809
4.
Demsky R, McCuaig J, Maganti M, Murphy KJ, Rosen B, Armel SR: Keeping it simple: genetics referrals for all invasive serous ovarian cancers. Gynecol Oncol. 2013, 130 (2): 329-333.CrossRefPubMed
5.
6.
Halperin R, Zehavi S, Langer R, Hadas E, Bukovsky I, Schneider D: Primary peritoneal serous papillary carcinoma: a new epidemiologic trend? A matched-case comparison with ovarian serous papillary cancer. Int J Gynecol Cancer. 2001, 11 (5): 403-408.CrossRefPubMed
7.
Davidson B, Smith Y, Nesland JM, Kaern J, Reich R, Trope CG: Defining a prognostic marker panel for patients with ovarian serous carcinoma effusion. Hum Pathol. 2013, 44 (11): 2449-2460.CrossRefPubMed
8.
Kim A, Ueda Y, Naka T, Enomoto T: Therapeutic strategies in epithelial ovarian cancer. J Exp Clin Canc Res: CR. 2012, 31: 14-CrossRef
9.
Zhang S, Mercado-Uribe I, Hanash S, Liu J: iTRAQ-based proteomic analysis of polyploid giant cancer cells and budding progeny cells reveals several distinct pathways for ovarian cancer development. PloS One. 2013, 8 (11): e80120-CrossRefPubMedPubMedCentral
10.
Zhang S, Mercado-Uribe I, Xing Z, Sun B, Kuang J, Liu J: Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Oncogene. 2014, 33 (1): 116-128.CrossRefPubMed
11.
Lee YH, Heo JH, Kim TH, Kang H, Kim G, Kim J, Cho SH, An HJ: Significance of cell cycle regulatory proteins as malignant and prognostic biomarkers in ovarian epithelial tumors. Int J Gynecol Pathol. 2011, 30 (3): 205-217.CrossRefPubMed
12.
Davidson B, Skrede M, Silins I, Shih Ie M, Trope CG, Florenes VA: Low-molecular weight forms of cyclin E differentiate ovarian carcinoma from cells of mesothelial origin and are associated with poor survival in ovarian carcinoma. Cancer. 2007, 110 (6): 1264-1271.CrossRefPubMed
13.
Alli E, Yang JM, Hait WN: Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene. 2007, 26 (7): 1003-1012.CrossRefPubMed
14.
Mistry SJ, Atweh GF: Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer. Mol Canc Therapeut. 2006, 5 (12): 3248-3257.CrossRef
15.
Sadow PM, Rumilla KM, Erickson LA, Lloyd RV: Stathmin expression in pheochromocytomas, paragangliomas, and in other endocrine tumors. Endocr Pathol. 2008, 19 (2): 97-103.CrossRefPubMed
16.
Wei SH, Lin F, Wang X, Gao P, Zhang HZ: Prognostic significance of stathmin expression in correlation with metastasis and clinicopathological characteristics in human ovarian carcinoma. Acta Histochem. 2008, 110 (1): 59-65.CrossRefPubMed
17.
Fuster JJ, Gonzalez JM, Edo MD, Viana R, Boya P, Cervera J, Verges M, Rivera J, Andres V: Tumor suppressor p27(Kip1) undergoes endolysosomal degradation through its interaction with sorting nexin 6. FASEB J. 2010, 24 (8): 2998-3009.CrossRefPubMed
18.
Deubzer HE, Ehemann V, Kulozik AE, Westermann F, Savelyeva L, Kopp-Schneider A, Riester D, Schwab M, Witt O: Anti-neuroblastoma activity of Helminthosporium carbonum (HC)-toxin is superior to that of other differentiating compounds in vitro. Cancer Lett. 2008, 264 (1): 21-28.CrossRefPubMed
19.
Chiappetta G, De Marco C, Quintiero A, Califano D, Gherardi S, Malanga D, Scrima M, Montero-Conde C, Cito L, Monaco M, Motti ML, Pasquinelli R, Agosti V, Robledo M, Fusco A, Viglietto G: Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer. Endocr Relat Cancer. 2007, 14 (2): 405-420.CrossRefPubMed
20.
Hung WC, Tseng WL, Shiea J, Chang HC: Skp2 overexpression increases the expression of MMP-2 and MMP-9 and invasion of lung cancer cells. Cancer Lett. 2010, 288 (2): 156-161.CrossRefPubMed
21.
Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, Silva EG: Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol. 2004, 28 (4): 496-504.CrossRefPubMed
22.
Zhang S, Mercado-Uribe I, Liu J: Tumor stroma and differentiated cancer cells can be originated directly from polyploid giant cancer cells induced by paclitaxel. Int J Cancer. 2014, 134 (3): 508-518.CrossRefPubMed
23.
Sun B, Qie S, Zhang S, Sun T, Zhao X, Gao S, Ni C, Wang X, Liu Y, Zhang L: Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors. Hum Pathol. 2008, 39 (3): 444-451.CrossRefPubMed
24.
Zhang S, Mercado-Uribe I, Liu J: Generation of erythroid cells from fibroblasts and cancer cells in vitro and in vivo. Cancer Lett. 2013, 333 (2): 205-212.CrossRefPubMedPubMedCentral
25.
Fang F, Orend G, Watanabe N, Hunter T, Ruoslahti E: Dependence of cyclin E-CDK2 kinase activity on cell anchorage. Science. 1996, 271 (5248): 499-502.CrossRefPubMed
26.
Scaltriti M, Eichhorn PJ, Cortes J, Prudkin L, Aura C, Jimenez J, Chandarlapaty S, Serra V, Prat A, Ibrahim YH, Guzman M, Gili M, Rodriguez O, Rodriguez S, Perez J, Green SR, Mai S, Rosen N, Hudis C, Baselga J: Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc Natl Acad Sci U S A. 2011, 108 (9): 3761-3766.CrossRefPubMedPubMedCentral
27.
Xiangming C, Natsugoe S, Takao S, Hokita S, Tanabe G, Baba M, Kuroshima K, Aikou T: The cooperative role of p27 with cyclin E in the prognosis of advanced gastric carcinoma. Cancer. 2000, 89 (6): 1214-1219.CrossRefPubMed
28.
Donnellan R, Chetty R: Cyclin E in human cancers. FASEB J. 1999, 13 (8): 773-780.PubMed
29.
Session DR, Lee GS, Choi J, Wolgemuth DJ: Expression of cyclin E in gynecologic malignancies. Gynecol Oncol. 1999, 72 (1): 32-37.CrossRefPubMed
30.
Demetrick DJ, Zhang H, Beach DH: Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2). Cytogenet Cell Genet. 1996, 73 (1–2): 104-107.CrossRefPubMed
31.
Deshaies RJ: SCF and Cullin/Ring H2-based ubiquitin ligases. Annu Rev Cell Dev Biol. 1999, 15: 435-467.CrossRefPubMed
32.
Koepp DM, Harper JW, Elledge SJ: How the cyclin became a cyclin: regulated proteolysis in the cell cycle. Cell. 1999, 97 (4): 431-434.CrossRefPubMed
33.
Imaki H, Nakayama K, Delehouzee S, Handa H, Kitagawa M, Kamura T, Nakayama KI: Cell cycle-dependent regulation of the Skp2 promoter by GA-binding protein. Cancer Res. 2003, 63 (15): 4607-4613.PubMed
34.
Sicari BM, Troxell R, Salim F, Tanwir M, Takane KK, Fiaschi-Taesch N: c-myc and skp2 coordinate p27 degradation, vascular smooth muscle proliferation, and neointima formation induced by the parathyroid hormone-related protein. Endocrinology. 2012, 153 (2): 861-872.CrossRefPubMed
35.
Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J, Slingerland J, Krek W: Skp2 is oncogenic and overexpressed in human cancers. Proc Natl Acad Sci U S A. 2001, 98 (9): 5043-5048.CrossRefPubMedPubMedCentral
36.
Fotovati A, Abu-Ali S, Nakayama K, Nakayama KI: Impaired ovarian development and reduced fertility in female mice deficient in Skp2. J Anat. 2011, 218 (6): 668-677.CrossRefPubMedPubMedCentral
37.
Belletti B, Nicoloso MS, Schiappacassi M, Berton S, Lovat F, Wolf K, Canzonieri V, D'Andrea S, Zucchetto A, Friedl P, Colombatti A, Baldassarre G: Stathmin activity influences sarcoma cell shape, motility, and metastatic potential. Mol Biol Cell. 2008, 19 (5): 2003-2013.CrossRefPubMedPubMedCentral
38.
Singer S, Malz M, Herpel E, Warth A, Bissinger M, Keith M, Muley T, Meister M, Hoffmann H, Penzel R, Gdynia G, Ehemann V, Schnabel PA, Kuner R, Huber P, Schirmacher P, Breuhahn K: Coordinated expression of stathmin family members by far upstream sequence element-binding protein-1 increases motility in non-small cell lung cancer. Cancer Res. 2009, 69 (6): 2234-2243.CrossRefPubMed
39.
Koutsami MK, Tsantoulis PK, Kouloukoussa M, Apostolopoulou K, Pateras IS, Spartinou Z, Drougou A, Evangelou K, Kittas C, Bartkova J, Bartek J, Gorgoulis VG: Centrosome abnormalities are frequently observed in non-small-cell lung cancer and are associated with aneuploidy and cyclin E overexpression. J Pathol. 2006, 209 (4): 512-521.CrossRefPubMed
40.
Deb-Basu D, Karlsson A, Li Q, Dang CV, Felsher DW: MYC can enforce cell cycle transit from G1 to S and G2 to S, but not mitotic cellular division, independent of p27-mediated inihibition of cyclin E/CDK2. Cell Cycle. 2006, 5 (12): 1348-1355.CrossRefPubMed
41.
Nelsen CJ, Hansen LK, Rickheim DG, Chen C, Stanley MW, Krek W, Albrecht JH: Induction of hepatocyte proliferation and liver hyperplasia by the targeted expression of cyclin E and skp2. Oncogene. 2001, 20 (15): 1825-1831.CrossRefPubMed
42.
Honnappa S, Jahnke W, Seelig J, Steinmetz MO: Control of intrinsically disordered stathmin by multisite phosphorylation. J Biol Chem. 2006, 281 (23): 16078-16083.CrossRefPubMed
43.
Steinmetz MO: Structure and thermodynamics of the tubulin-stathmin interaction. J Struct Biol. 2007, 158 (2): 137-147.CrossRefPubMed
44.
Baldassarre G, Belletti B, Nicoloso MS, Schiappacassi M, Vecchione A, Spessotto P, Morrione A, Canzonieri V, Colombatti A: p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion. Cancer Cell. 2005, 7 (1): 51-63.CrossRefPubMed
Metadata
Title
Polyploid giant cancer cells with budding and the expression of cyclin E, S-phase kinase-associated protein 2, stathmin associated with the grading and metastasis in serous ovarian tumor
Authors
Hongcheng Lv
Yang Shi
Li Zhang
Dan Zhang
Guang Liu
Zhengduo Yang
Yan Li
Fei Fei
Shiwu Zhang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-576

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