DOI QR코드

DOI QR Code

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

  • Zhou, Lei (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Yu, Lan (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Feng, Zhen-Zhong (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Gong, Xiao-Meng (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Cheng, Ze-Nong (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Yao, Nan (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Wang, Dan-Na (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College) ;
  • Wu, Shi-Wu (Department of Pathology, the First Hospital Affiliated to Bengbu Medical College, Bengbu Medical College)
  • Published : 2015.06.03

Abstract

Background: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. Materials and Methods: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. Results: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was $21.7{\pm}11.1$ in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (${\geq}22$) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). Conclusions: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.

Keywords

References

  1. Ahmadi SA, Moinfar M, Gohari Moghaddam K, Bahadori M (2010). Practical application of angiogenesis and vasculogenic mimicry in prostatic adenocarcinoma. Arch Iran Med, 13, 498-503.
  2. Amsterdam A, Raanan C, Schreiber L, Polin N, Givol D (2013). LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer. Biochem Biophys Res Commun, 433, 157-62. https://doi.org/10.1016/j.bbrc.2013.02.038
  3. Barker N, Huch M, Kujala P, et al (2010). Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell, 6, 25-36. https://doi.org/10.1016/j.stem.2009.11.013
  4. Bu Z, Zheng Z, Zhang L, et al (2013). LGR5 is a promising biomarker for patients with stage I and II gastric cancer. Chin J Cancer Res, 25, 79-89.
  5. Curley MD, Therrien VA, Cummings CL, et al (2009). CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells. 27, 2875-83.
  6. Economopoulou P, Kaklamani VG, Siziopikou K (2012). The role of cancer stem cells in breast cancer initiation and progression, potential cancer stem cell-directed therapies. The oncologist. 17, 1394-401. https://doi.org/10.1634/theoncologist.2012-0163
  7. EI Hallani S, Boisselier B, Peglion F, et al (2010). A new alternative mechanism in glioblastoma vascularization, tubular vasculogenic mimicry. Brain, 133, 973-982. https://doi.org/10.1093/brain/awq044
  8. Femia AP, Dolara P, Salvadori M, Caderni G (2013). Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazineinduced rat colon carcinogenesis, correlation with nuclear ${\beta}$-catenin. BMC Cancer, 13, 48. https://doi.org/10.1186/1471-2407-13-48
  9. Flesken-Nikitin A, Hwang CI, Cheng CY, et al (2013). Ovarian surface epithelium at the junction area contains a cancerprone stem cell niche. Nature, 495, 241-5. https://doi.org/10.1038/nature11979
  10. Fu D, He X, Yang S, et al (2011). Zoledronic acid inhibits vasculogenic mimicry in murine osteosarcoma cell line in vitro. BMC Musculoskelet Disord, 12, 146. https://doi.org/10.1186/1471-2474-12-146
  11. Hashimoto K, Aoyagi K, Isobe T, Kouhuji K, Shirouzu K (2014). Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer. Gastric Cancer, 17, 97-106. https://doi.org/10.1007/s10120-013-0255-9
  12. Hendrix MJ, Seftor EA, Hess AR, Seftor RE (2003). Vasculogenic mimicry and tumour-cell plasticity, lessons from melanoma. Nat Rev Cancer, 3, 411-21. https://doi.org/10.1038/nrc1092
  13. Hilbe W, Dirnhofer S, Oberwasserlechner F, et al (2004). CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer. J Clin Pathol, 57, 965-9. https://doi.org/10.1136/jcp.2004.016444
  14. Huang J, Chen K, Gong W, Dunlop NM, Wang JM (2008). G-protein coupled chemoattractant receptors and cancer. Front Biosci, 13, 3352-63.
  15. Immervoll H, Hoem D, Sakariassen PO, Steffensen OJ, Molven A (2008). Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer, 8, 48. https://doi.org/10.1186/1471-2407-8-48
  16. Jiang J, Liu W, Guo X, et al (2011). IRX1 influences peritoneal spreading and metastasis via inhibiting BDKRB2-dependent neovascularization on gastric cancer. Oncogene, 30, 4498-508. https://doi.org/10.1038/onc.2011.154
  17. Li M, Gu Y, Zhang Z, et al (2010). Vasculogenic mimicry, a new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res, 16, 259-66. https://doi.org/10.1007/s12253-009-9220-7
  18. Lin KK, Andersen B (2008). Have hair follicle stem cells shed their tranquil image? Cell Stem Cell, 3, 581-2. https://doi.org/10.1016/j.stem.2008.11.005
  19. Liu TJ, Sun BC, Zhao XL, et al (2013). CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene, 32, 544-53. https://doi.org/10.1038/onc.2012.85
  20. Liu Z, Dai W, Jiang L, Cheng Y (2014). Over-expression of LGR5 correlates with poor survival of colon cancer in mice as well as in patients. Neoplasma, 61, 177-85. https://doi.org/10.4149/neo_2014_016
  21. Long H, Xiang T, Qi W, et al (2015). CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition. Oncotarget. [Epub ahead of print].
  22. Long H, Xie R, Xiang T, et al (2012). Autocrine CCL5 signaling promotes invasion and migration of CD133+ ovarian cancer stem-like cells via NF-kappaB-mediated MMP-9 upregulation. Stem Cells, 30, 2309- 19. https://doi.org/10.1002/stem.1194
  23. Malanchi I, Santamaria-Martinez A, Susanto E, et al (2012). Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 481, 85-9. https://doi.org/10.1038/nature10694
  24. Maniotis AJ, Folberg R, Hess A, et al (1999). Vascular channel formation by human melanoma cells in vivo and in vitro, vasculogenic mimicry. Am J Pathol, 155, 739-752. https://doi.org/10.1016/S0002-9440(10)65173-5
  25. McClanahan T, Koseoglu S, Smith K, et al (2006). Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors. Cancer Biol Ther, 5, 419-26. https://doi.org/10.4161/cbt.5.4.2521
  26. Miraglia S, Godfrey W, Yin AH, et al (1997). A novel fivetransmembrane hematopoietic stem cell antigen, isolation, characterization, and molecular cloning. Blood, 90, 5013-21.
  27. O'Brien CA, Pollett A, Gallinger S, Dick JE (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 445, 106-110. https://doi.org/10.1038/nature05372
  28. Peichev M, Naiyer AJ, Pereira D, et al (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood, 95, 952-8.
  29. Rosen JM, Jordan CT (2009). The increasing complexity of the cancer stem cell paradigm. Science, 324, 1670-3. https://doi.org/10.1126/science.1171837
  30. Sato T, Clevers H (2013). Growing self-organizing miniguts from a single intestinal stem cell, mechanism and applications. Science, 340, 1190-4. https://doi.org/10.1126/science.1234852
  31. Schneider M, Huber J, Hadaschik B, et al (2012). Characterization of colon cancer cells, a functional approach characterizing CD133 as a potential stem cell marker. BMC Cancer, 12, 96. https://doi.org/10.1186/1471-2407-12-96
  32. Scully S, Francescone R, Faibish M, et al (2012). Transdifferentiation of glioblastoma stem-like cells into mural cells drives vasculogenic mimicry in glioblastomas. J Neurosci, 32, 12950-60. https://doi.org/10.1523/JNEUROSCI.2017-12.2012
  33. Shirakawa K, Wakasugi H, Heike Y, et al (2002). Vasculogenic mimicry and pseudo-comedo formation in breast cancer. Int J Cancer, 99, 821-8. https://doi.org/10.1002/ijc.10423
  34. Singh SK, Hawkins C, Clarke ID, et al (2004). Identification of human brain tumour initiating cells. Nature, 432, 396-401. https://doi.org/10.1038/nature03128
  35. Steg AD, Bevis KS, Katre AA, et al (2012). Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res, 18, 869-81. https://doi.org/10.1158/1078-0432.CCR-11-2188
  36. Sun B, Qie S, Zhang S, et al (2008). Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors. Hum Pathol, 39, 445-51.
  37. Sun B, Zhang S, Zhao X, Zhang W, Hao X (2004). Vasculogenic mimicry is associated with poor survival in patients with mesothelial sarcomas and alveolar rhabdomyosarcomas. Int J Oncol, 25, 1609-14.
  38. Sun D, Sun B, Liu T, et al (2013). Slug promoted vasculogenic mimicry in hepatocellular carcinoma. J Cell Mol Med, 17, 1038-47. https://doi.org/10.1111/jcmm.12087
  39. Sun W, Fan YZ, Zhang WZ, Ge CY (2011). A pilot histomorphology and hemodynamic of vasculogenic mimicry in gallbladder carcinomas in vivo and in vitro. J Exp Clin Cancer Res, 30, 46. https://doi.org/10.1186/1756-9966-30-46
  40. Tang HS, Feng YJ, Yao LQ (2009). Angiogenesis, vasculogenesis, and vasculogenic mimicry in ovarian cancer. Int J Gynecol Cancer, 19, 605-10. https://doi.org/10.1111/IGC.0b013e3181a389e6
  41. Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65, 87-108. https://doi.org/10.3322/caac.21262
  42. Valyi-Nagy K, Kormos B, Ali M, Shukla D, Valyi-Nagy T (2012). Stem cell marker CD271 is expressed by vasculogenic mimicry-forming uveal melanoma cells in three-dimensional cultures. Mol Vis, 18, 588-92.
  43. Vermeulen L, Todaro M, de Sousa Mello F, et al (2008). Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA, 105, 13427-32. https://doi.org/10.1073/pnas.0805706105
  44. Wu S, Yu L, Wang D, et al (2012). Aberrant expression of CD133 in non-small cell lung cancer and its relationship to vasculogenic mimicry. BMC Cancer, 12, 535. https://doi.org/10.1186/1471-2407-12-535
  45. Wu XS, Xi HQ, Chen L (2012). Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival. World J Surg Oncol, 10, 244. https://doi.org/10.1186/1477-7819-10-244
  46. Yan X, Ma L, Yi D, et al (2011). A CD133-related gene expression signature identifies an aggressive glioblastoma subtype with excessive mutations. Proc Natl Acad Sci U S A, 108, 1591-6. https://doi.org/10.1073/pnas.1018696108
  47. Yang L, Levi E, Zhu S, Du J, Majumdar AP (2013). Cancer stem cells biomarkers in gastric carcinogenesis. J Gastrointest Cancer, 44, 428-35. https://doi.org/10.1007/s12029-013-9534-2
  48. Yao X, Ping Y, Liu Y, et al (2013). Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a key role in vasculogenic mimicry formation, neovascularization and tumor initiation by Glioma stem-like cells. PLoS One, 8, 57188. https://doi.org/10.1371/journal.pone.0057188
  49. Yin AH, Miraglia S, Zanjani ED, et al (1997). AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood, 90, 5002-12.
  50. Zarkoob H, Taube JH, Singh SK, Mani SA, Kohandel M (2013). Investigating the link between molecular subtypes of glioblastoma epithelial-mesenchymal transition and CD133 cell surface protein. PLoS One, 8, 64169. https://doi.org/10.1371/journal.pone.0064169
  51. Zhang D, Sun B, Zhao X, et al (2014). Twist1 expression induced by sunitinib accelerates tumor cell vasculogenic mimicry by increasing the population of CD133+ cells in triple-negative breast cancer. Mol Cancer, 13, 207. https://doi.org/10.1186/1476-4598-13-207
  52. Zhang Y, Sun B, Zhao X, et al (2013). Clinical significances and prognostic value of cancer stem-like cells markers and vasculogenic mimicry in renal cell carcinoma. J Surg Oncol, 49, 3914-23.
  53. Zhao P, Li Y, Lu Y (2010). Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma. BMC Cancer, 10, 218. https://doi.org/10.1186/1471-2407-10-218
  54. Zhu L, Gibson P, Currle DS, et al (2009). Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature, 457, 603-7. https://doi.org/10.1038/nature07589

Cited by

  1. Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta-analysis vol.19, pp.2, 2016, https://doi.org/10.1007/s10456-016-9500-2
  2. -positive cancer cells in intramucosal gastric signet-ring cell carcinoma vol.66, pp.9, 2016, https://doi.org/10.1111/pin.12451
  3. Clinicopathological and prognostic significance of cancer stem cell markers CD44 and CD133 in patients with gastric cancer vol.95, pp.42, 2016, https://doi.org/10.1097/MD.0000000000005163
  4. Correlation Between Tumor Vasculogenic Mimicry and Poor Prognosis of Human Digestive Cancer Patients: A Systematic Review and Meta-Analysis pp.1532-2807, 2019, https://doi.org/10.1007/s12253-018-0496-3