Advertisement

Tumor Biology

, Volume 34, Issue 6, pp 3981–3987 | Cite as

Elevated expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP is a novel indicator for lymph node and peritoneal metastasis of epithelial ovarian cancer patients

  • Hongyang Yu
  • Qian Liu
  • Tao Xin
  • Lina Xing
  • Guanglu Dong
  • Qiuying Jiang
  • Yanju Lv
  • Xiaowei Song
  • Chong Teng
  • Dayong Huang
  • Yanju Li
  • Weixi Shen
  • Chong Teng
  • Yinghua Jin
  • Fubin Zhang
Research Article

Abstract

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors’ knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5 %) presented peritoneal metastases and 43 (48.3 %) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95 % confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95 % CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.

Keywords

Hyaluronan acid binding protein 1 (HABP1) Peritoneal dissemination Lymph node metastasis Epithelial ovarian cancer (EOC) 

Notes

Acknowledgments

The authors gratefully acknowledge the financial supports from the Doctoral Research Fund of the Second Affiliated Hospital of Harbin Medical University (Hongyang Yu) and Foundation of Heilongjiang department of education (No. 12531387), Heilongjiang Provincial Health Office (No. 2012–625), and Youth Science Foundation of Heilongjiang Province (No. QC2010078, QC2011C017). We also thank Hui Cheng (The Third Affiliated (Tumor) Hospital of Harbin Medical University) for her IHC assistance.

Conflicts of interest

None

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351:2519–29.PubMedCrossRefGoogle Scholar
  3. 3.
    Amadori D, Sansoni E, Amadori A. Ovarian cancer: natural history and metastatic pattern. Front Biosci. 1997;2:g8–g10.PubMedGoogle Scholar
  4. 4.
    Ozols RF, Bookman MA, Connolly DC, et al. Focus on epithelial ovarian cancer. Cancer Cell. 2004;5:19–24.PubMedCrossRefGoogle Scholar
  5. 5.
    Fagotti A, Gallotta V, Romano F, et al. Peritoneal carcinosis of ovarian origin. World J Gastrointest Oncol. 2010;5:102–8.CrossRefGoogle Scholar
  6. 6.
    Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol. 2009;112:265–74.PubMedCrossRefGoogle Scholar
  7. 7.
    Mitrus I, Bryndza E, Sochanik A, Szala S. Evolving models of tumor origin and progression. Tumour Biol. 2012;33:911–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Ricciardelli C. Extracellular matrix of ovarian tumors. Semin Reprod Med. 2006;24:270–82.PubMedCrossRefGoogle Scholar
  9. 9.
    Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411:375–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Gardner MJ, Catterall JB, Jones LM, et al. Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible step in peritoneal metastasis. Clin Exp Metastasis. 1996;14:325–34.PubMedCrossRefGoogle Scholar
  11. 11.
    Jones LM, Gardner MJ, Catterall JB, et al. Hyaluronic acid secreted by mesothelial cells: a natural barrier to ovarian cancer cell adhesion. Clin Exp Metastasis. 1995;13:373–80.PubMedGoogle Scholar
  12. 12.
    Tzuman YC, Sapoznik S, Granot D, et al. Peritoneal adhesion and angiogenesis in ovarian carcinoma are inversely regulated by hyaluronan: the role of gonadotropins. Neoplasia. 2010;12:51–60.PubMedGoogle Scholar
  13. 13.
    Ween MP, Hummitzsch K, Rodgers RJ, et al. Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides. Clin Exp Metastasis. 2011;28:113–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Casey RC, Koch KA, Oegema Jr TR, et al. Establishment of an in vitro assay to measure the invasion of ovarian carcinoma cells through mesothelial cell monolayers. Clin Exp Metastasis. 2003;20:343–56.PubMedCrossRefGoogle Scholar
  15. 15.
    Banzato A, Bobisse S, Rondina M, et al. A paclitaxel-hyaluronan bioconjugate targeting ovarian cancer affords a potent in vivo therapeutic activity. Clin Cancer Res. 2008;14:3598–606.PubMedCrossRefGoogle Scholar
  16. 16.
    Majumdar M, Datta K. Assignment of cDNA encoding hyaluronic acid-binding protein 1 to human chromosome 17p12–p13. Genomics. 1998;51:476–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Deb TB, Datta K. Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32. A protein co-purified with splicing factor SF2. J Biol Chem. 1996;271:2206–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Krainer AR, Mayeda A, Kozak D, et al. Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins. U170K and Drosophila splicing regulators. Cell. 1991;66:383–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Gupta S, Datta K. Possible role of hyaluronectin on cell adhesion in rat histiocytoma. Exp Cell Res. 1991;195:386–94.PubMedCrossRefGoogle Scholar
  20. 20.
    Ranganathan S, Ganguly AK, Datta K. Evidence for presence of hyaluronan binding protein on spermatozoa and its possible involvement in sperm function. Mol Reprod Dev. 1994;38:69–76.PubMedCrossRefGoogle Scholar
  21. 21.
    Das S, Deb TB, Kumar R, et al. Multifunctional activities of human fibroblast 34-kDa hyaluronic acid-binding protein. Gene. 1997;190:223–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Gupta S, Batchu RB, Datta K. Purification partial characterization of rat kidney hyaluronic acid binding protein and its localization on the cell surface. Eur J Cell Biol. 1991;56:58–67.PubMedGoogle Scholar
  23. 23.
    Rao CM, Deb TB, Datta K. Hyaluronic acid induced hyaluronic acid binding protein phosphorylation and inositol triphosphate formation in lymphocytes. Biochem Mol Biol Int. 1996;40:327–37.PubMedGoogle Scholar
  24. 24.
    Rao CM, Deb TB, Gupta S, et al. Regulation of cellular phosphorylation of hyaluronan binding protein and its role in the formation of second messenger. Biochim Biophys Acta. 1997;1336:387–93.PubMedCrossRefGoogle Scholar
  25. 25.
    Itahana K, Zhang Y. Mitochondrial p32 is a critical mediator of ARF-induced apoptosis. Cancer Cell. 2008;13:542–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Reef S, Shifman O, Oren M, et al. The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein. Oncogene. 2007;26:6677–83.PubMedCrossRefGoogle Scholar
  27. 27.
    Xin T, Zhang F, Jiang Q, Chen C, Huang D, Li Y, et al. Extraction, purification and antitumor activity of a water-soluble polysaccharide from the roots of Polygala tenuifolia. Carbohydr Polym. 2012;90:1127–31.PubMedCrossRefGoogle Scholar
  28. 28.
    Yoo HJ, Lee JS, Ko YG. Cell-surface gC1qR is a key regulator for lamellipodia formation and cancer metastasis. J Biol Chem. 2011;286:23093–101.PubMedCrossRefGoogle Scholar
  29. 29.
    Amamoto R, Yagi M, Song Y, et al. Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter prostate-specific antigen relapse time after radical prostatectomy. Cancer Sci. 2011;102:639–47.PubMedCrossRefGoogle Scholar
  30. 30.
    Ghosh I, Chowdhury AR, Rajeswari MR, et al. Differential expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP during progression of epidermal carcinoma. Mol Cell Biochem. 2004;267:133–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Prakash M, Kale S, Ghosh I, Kundu GC, Datta K. Hyaluronan-binding protein 1 (HABP1/p32/gC1qR) induces melanoma cell migration and tumor growth by NF-kappa B dependent MMP-2 activation through integrin α(v)β(3) interaction. Cell Signal. 2011;23:1563–77.PubMedCrossRefGoogle Scholar
  32. 32.
    Rubinstein DB, Stortchevoi A, Boosalis M, et al. Receptor for the globular heads of C1q (gC1q-R. p33. hyaluronan-binding protein) is preferentially expressed by adenocarcinoma cells. Int J Cancer. 2004;110:741–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Fogal V, Zhang L, Krajewski S, et al. Mitochondrial/cell-surface protein p32/gC1qR as a molecular target in tumor cells and tumor stroma. Cancer Res. 2008;68:7210–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Kamal A, Datta K. Upregulation of hyaluronan binding protein 1 (HABP1/p32/gC1qR) is associated with cisplatin induced apoptosis. Apoptosis. 2006;11:861–74.PubMedCrossRefGoogle Scholar
  35. 35.
    Scully R. Histological typing of ovarian tumors (WHO. World Health Organization. International Histological Classification of Tumours). Berlin: Springer; 1999.CrossRefGoogle Scholar
  36. 36.
    Benedet JL, Bender H, Jones H, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2000;70:209–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Yu G, Wang J. Significance of hyaluronan binding protein (HABP1/P32/gC1qR) expression in advanced serous ovarian cancer patients. Exp Mol Pathol. 2013;94:210–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Kitazawa S, Takenaka A, Kondo T, et al. Protruding disordered loop of gC1qR is specifically exposed and related to antiapoptotic property in germ cell lineage. Histochem Cell Biol. 2006;126:665–77.PubMedCrossRefGoogle Scholar
  39. 39.
    Dang CV. p32 (C1QBP) and cancer cell metabolism: is the Warburg effect a lot of hot air? Mol Cell Biol. 2010;30:1300–2.PubMedCrossRefGoogle Scholar
  40. 40.
    Sengupta A, Banerjee B, Tyagi RK, et al. Golgi localization and dynamics of hyaluronan binding protein 1 (HABP1/p32/C1QBP) during the cell cycle. Cell Res. 2005;15:183–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Storz P, Hausser A, Link G, et al. Protein kinase C is regulated by the multifunctional chaperon protein p32. J Biol Chem. 2000;275:24601–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Kaul R, Saha P, Saradhi M, Prasad RL, Chatterjee S, Ghosh I, et al. Overexpression of hyaluronan-binding protein 1 (HABP1/p32/gC1qR) in HepG2 cells leads to increased hyaluronan synthesis and cell proliferation by up-regulation of cyclin D1 in AKT-dependent pathway. J Biol Chem. 2012;287:19750–64.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Hongyang Yu
    • 1
  • Qian Liu
    • 2
  • Tao Xin
    • 3
  • Lina Xing
    • 1
  • Guanglu Dong
    • 1
  • Qiuying Jiang
    • 3
  • Yanju Lv
    • 3
  • Xiaowei Song
    • 3
  • Chong Teng
    • 3
  • Dayong Huang
    • 3
  • Yanju Li
    • 3
  • Weixi Shen
    • 3
  • Chong Teng
    • 3
  • Yinghua Jin
    • 3
  • Fubin Zhang
    • 4
  1. 1.Department of Radiation OncologyThe Secound Affiliated Hospital, Harbin Medical UniversityHarbinChina
  2. 2.Department of Obstetrics and GynecologyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of Medical OncologyThe Second Affiliated Hospital, Harbin Medical UniversityHarbinChina
  4. 4.Department of GynecologyThe Third Affiliated (Tumor) Hospital, Harbin Medical UniversityHarbinChina

Personalised recommendations