Skip to main content

Advertisement

SpringerLink
Log in

High scavenger receptor class B type I expression is related to tumor aggressiveness and poor prognosis in breast cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

Scavenger receptor class B type I (SR-BI) has been linked to the development and progression of breast cancer. However, its clinical significance in breast cancer remains unclear. Here, we evaluated SR-BI expression in a well-characterized breast cancer tissue microarray by immunohistochemistry. High SR-BI expression was observed in 54 % of all breast cancer cases and was significantly associated with advanced pTNM stage (P = 0.002), larger tumor size (P = 0.023), lymph node metastasis (P = 0.012), and the absence of ER (P = 0.014). The Kaplan–Meier survival analysis revealed that patients with high SR-BI expression had significantly shorter overall survival (OS) (P = 0.004). Moreover, multivariate analysis with adjustment for other prognostic factors confirmed that SR-BI was an independent prognostic factor for patient outcome (P = 0.017). Overall, our study demonstrated that high SR-BI expression was related to conventional parameters indicative of more aggressive tumor type and may serve as a new prognostic marker for poor clinical outcome in human breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  2. Bray F, McCarron P, Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 2004;6(6):229–39.

    Article  PubMed  PubMed Central  Google Scholar 

  3. de Lorgeril M, Salen P. Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related lifestyle factors. BMC Med. 2014;12:54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Thompson HJ, Sedlacek SM, Paul D, Wolfe P, McGinley JN, Playdon MC, et al. Effect of dietary patterns differing in carbohydrate and fat content on blood lipid and glucose profiles based on weight-loss success of breast-cancer survivors. Breast Cancer Res. 2012;14(1):R1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Muntoni S, Atzori L, Mereu R, Satta G, Macis MD, Congia M, et al. Serum lipoproteins and cancer. Nutr Metab Cardiovasc Dis. 2009;19(3):218–25.

    Article  CAS  PubMed  Google Scholar 

  6. Calvo D, Vega MA. Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family. J Biol Chem. 1993;268(25):18929–35.

    CAS  PubMed  Google Scholar 

  7. Murao K, Terpstra V, Green SR, Kondratenko N, Steinberg D, Quehenberger O. Characterization of CLA-1, a Human Homologue of Rodent Scavenger Receptor BI, as a Receptor for High Density Lipoprotein and Apoptotic Thymocytes. J Biol Chem. 1997;272(28):17551–7.

    Article  CAS  PubMed  Google Scholar 

  8. Cao G, Garcia CK, Wyne KL, Schultz RA, Parker KL, Hobbs HH. Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor 1. J Biol Chem. 1997;272(52):33068–76.

    Article  CAS  PubMed  Google Scholar 

  9. Cao WM, Murao K, Imachi H, Yu X, Abe H, Yamauchi A, et al. A mutant high-density lipoprotein receptor inhibits proliferation of human breast cancer cells. Cancer Res. 2004;64(4):1515–21.

    Article  CAS  PubMed  Google Scholar 

  10. Krieger M. Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Investig. 2001;108(6):793–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Guo L, Song Z, Li M, Wu Q, Wang D, Feng H, et al. Scavenger Receptor BI Protects against Septic Death through Its Role in Modulating Inflammatory Response. J Biol Chem. 2009;284(30):19826–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li Y, Kakinami C, Li Q, Yang B, Li H. Human apolipoprotein A-I is associated with dengue virus and enhances virus infection through SR-BI. PLoS One. 2013;8(7), e70390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. McGrowder D, Riley C, Morrison EY, Gordon L: The role of high-density lipoproteins in reducing the risk of vascular diseases, neurogenerative disorders, and cancer. Cholesterol 2011, 2011:496925.

  14. Vilchez JA, Martinez-Ruiz A, Sancho-Rodriguez N, Martinez-Hernandez P, Noguera-Velasco JA. The real role of prediagnostic high-density lipoprotein cholesterol and the cancer risk: a concise review. Eur J Clin Invest. 2014;44(1):103–14.

    Article  CAS  PubMed  Google Scholar 

  15. Wadsack C, Hirschmugl B, Hammer A, Levak-Frank S, Kozarsky KF, Sattler W, et al. Scavenger receptor class B, type I on non-malignant and malignant human epithelial cells mediates cholesteryl ester-uptake from high density lipoproteins. Int J Biochem Cell Biol. 2003;35(4):441–54.

    Article  CAS  PubMed  Google Scholar 

  16. Leon CG, Locke JA, Adomat HH, Etinger SL, Twiddy AL, Neumann RD, et al. Alterations in cholesterol regulation contribute to the production of intratumoral androgens during progression to castration-resistant prostate cancer in a mouse xenograft model. Prostate. 2010;70(4):390–400.

    CAS  PubMed  Google Scholar 

  17. Shahzad MMK, Mangala LS, Han HD, Lu C, Bottsford-Miller J, Nishimura M, et al. Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles. Neoplasia. 2011;13(4):309–IN308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zheng Y, Liu Y, Jin H, Pan S, Qian Y, Huang C, et al. Scavenger receptor B1 is a potential biomarker of human nasopharyngeal carcinoma and its growth is inhibited by HDL-mimetic nanoparticles. Theranostics. 2013;3(7):477–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Danilo C, Gutierrez-Pajares JL, Mainieri MA, Mercier I, Lisanti MP, Frank PG. Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development. Breast Cancer Res. 2013;15(5):R87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Remmele W, Stegner HE. [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe. 1987;8(3):138–40.

    CAS  PubMed  Google Scholar 

  21. Llaverias G, Danilo C, Mercier I, Daumer K, Capozza F, Williams TM, et al. Role of cholesterol in the development and progression of breast cancer. Am J Pathol. 2011;178(1):402–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Danilo C, Frank PG. Cholesterol and breast cancer development. Curr Opin Pharmacol. 2012;12(6):677–82.

    Article  CAS  PubMed  Google Scholar 

  23. Pussinen PJ, Karten B, Wintersperger A, Reicher H, McLean M, Malle E, et al. The human breast carcinoma cell line HBL-100 acquires exogenous cholesterol from high-density lipoprotein via CLA-1 (CD-36 and LIMPII analogous 1)-mediated selective cholesteryl ester uptake. Biochem J. 2000;349(Pt 2):559–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pan B, Ren H, Lv X, Zhao Y, Yu B, He Y, et al. Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis. J Transl Med. 2012;10:65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pan B, Ren H, Ma Y, Liu D, Yu B, Ji L, et al. High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells. Int J Cancer. 2012;131(1):70–82.

    Article  CAS  PubMed  Google Scholar 

  26. Saddar S, Carriere V, Lee WR, Tanigaki K, Yuhanna IS, Parathath S, et al. Scavenger receptor class B type I is a plasma membrane cholesterol sensor. Circ Res. 2013;112(1):140–51.

    Article  CAS  PubMed  Google Scholar 

  27. Silver DL, Tall AR. The cellular biology of scavenger receptor class B type I. Curr Opin Lipidol. 2001;12(5):497–504.

    Article  CAS  PubMed  Google Scholar 

  28. Antalis CJ, Arnold T, Rasool T, Lee B, Buhman KK, Siddiqui RA. High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation. Breast Cancer Res Treat. 2010;122(3):661–70.

    Article  CAS  PubMed  Google Scholar 

  29. Yuhanna IS, Zhu Y, Cox BE, Hahner LD, Osborne-Lawrence S, Lu P, et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med. 2001;7(7):853–7.

    Article  CAS  PubMed  Google Scholar 

  30. Martin JH, Begum S Fau - Alalami O, Alalami O Fau - Harrison A, Harrison A Fau - Scott KW, Scott KW: Endothelial nitric oxide synthase: correlation with histologic grade, lymph node status and estrogen receptor expression in human breast cancer. (1010–4283 (Print)).

  31. Loibl S, Strank C, von Minckwitz G, Sinn HP, Buck A, Solbach C, et al. Immunohistochemical evaluation of endothelial nitric oxide synthase expression in primary breast cancer. Breast. 2005;14(3):230–5.

    Article  CAS  PubMed  Google Scholar 

  32. Fukumura D, Kashiwagi S, Jain RK. The role of nitric oxide in tumour progression. Nat Rev Cancer. 2006;6(7):521–34.

    Article  CAS  PubMed  Google Scholar 

  33. Lahdenranta J, Hagendoorn J, Padera TP, Hoshida T, Nelson G, Kashiwagi S, et al. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis. Cancer Res. 2009;69(7):2801–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Nakao K, et al. Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res. 2006;12(4):1201–7.

    Article  CAS  PubMed  Google Scholar 

  35. Lacko AG, Nair M, Paranjape S, Johnso S, McConathy WJ. High density lipoprotein complexes as delivery vehicles for anticancer drugs. Anticancer Res. 2002;22(4):2045–9.

    CAS  PubMed  Google Scholar 

  36. Medina-Echeverz J, Fioravanti J, Diaz-Valdes N, Frank K, Aranda F, Gomar C, et al. Harnessing high density lipoproteins to block transforming growth factor beta and to inhibit the growth of liver tumor metastases. PLoS One. 2014;9(5), e96799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yang S, Damiano MG, Zhang H, Tripathy S, Luthi AJ, Rink JS, et al. Biomimetic, synthetic HDL nanostructures for lymphoma. Proc Natl Acad Sci U S A. 2013;110(7):2511–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. McConathy WJ, Nair MP, Paranjape S, Mooberry L, Lacko AG. Evaluation of synthetic/reconstituted high-density lipoproteins as delivery vehicles for paclitaxel. Anticancer Drugs. 2008;19(2):183–8.

    Article  CAS  PubMed  Google Scholar 

  39. Mooberry LK, Nair M, Paranjape S, McConathy WJ, Lacko AG. Receptor mediated uptake of paclitaxel from a synthetic high density lipoprotein nanocarrier. J Drug Target. 2010;18(1):53–8.

    Article  CAS  PubMed  Google Scholar 

  40. Han J, Parsons M, Zhou X, Nicholson AC, Gotto Jr AM, Hajjar DP. Functional interplay between the macrophage scavenger receptor class B type I and pitavastatin (NK-104). Circulation. 2004;110(22):3472–9.

    Article  CAS  PubMed  Google Scholar 

  41. Zhao SP, Wu ZH, Hong SC, Ye HJ, Wu J. Effect of atorvastatin on SR-BI expression and HDL-induced cholesterol efflux in adipocytes of hypercholesterolemic rabbits. Clin Chim Acta; Int J Clin Chem. 2006;365(1–2):119–24.

    Article  CAS  Google Scholar 

  42. Tsuruoka H, Khovidhunkit W, Brown BE, Fluhr JW, Elias PM, Feingold KR. Scavenger receptor class B type I is expressed in cultured keratinocytes and epidermis. Regulation in response to changes in cholesterol homeostasis and barrier requirements. J Biol Chem. 2002;277(4):2916–22.

    Article  CAS  PubMed  Google Scholar 

  43. Kimura T, Mogi C, Tomura H, Kuwabara A, Im DS, Sato K, et al. Induction of Scavenger Receptor Class B Type I Is Critical for Simvastatin Enhancement of High-Density Lipoprotein-Induced Anti-Inflammatory Actions in Endothelial Cells. J Immunol. 2008;181(10):7332–40.

    Article  CAS  PubMed  Google Scholar 

  44. Briand F, Magot T Fau - Krempf M, Krempf M Fau - Nguyen P, Nguyen P Fau - Ouguerram K, Ouguerram K: Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs. (0014–2972 (Print)).

  45. de Haan W, van der Hoogt CC, Westerterp M, Hoekstra M, Dallinga-Thie GM, Princen HM, et al. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice. Atherosclerosis. 2008;197(1):57–63.

    Article  CAS  PubMed  Google Scholar 

  46. Mardones P, Pilon A, Bouly M, Duran D, Nishimoto T, Arai H, et al. Fibrates down-regulate hepatic scavenger receptor class B type I protein expression in mice. J Biol Chem. 2003;278(10):7884–90.

    Article  CAS  PubMed  Google Scholar 

  47. Lan D, Silver DL. Fenofibrate induces a novel degradation pathway for scavenger receptor B-I independent of PDZK1. J Biol Chem. 2005;280(24):23390–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Cancer Center, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, China

      Baoying Yuan, Xingwen Wang, Huiling Liu, Junqing Han & Hong Feng

    2. Department of Orthopedics, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, China

      Changshun Wu

    3. Department of Central Lab, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, China

      Ling Guo

    4. Department of Pediatrics, Saha Cardiovascular Research Center, University of Kentucky College of Medicine, 741 S. Limestone Street, Lexington, KY, 40536, USA

      Dan Wang & Xiang-An Li

    Authors
    1. Baoying Yuan
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Changshun Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Xingwen Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Dan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Huiling Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Ling Guo
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Xiang-An Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Junqing Han
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Hong Feng
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Xiang-An Li, Junqing Han or Hong Feng.

    Additional information

    This work was supported by grants from the National Natural Science Foundation of China (No. 81201865 and 81202307), and Shandong Science and Technology Development Planning (No. 2011GSF11843 and 2012G0021822).

    Baoying Yuan and Changshun Wu contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    ESM 1

    (DOCX 228 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Yuan, B., Wu, C., Wang, X. et al. High scavenger receptor class B type I expression is related to tumor aggressiveness and poor prognosis in breast cancer. Tumor Biol. 37, 3581–3588 (2016). https://doi.org/10.1007/s13277-015-4141-4

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-015-4141-4

    Keywords

    Search

    Navigation