Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.10.4177

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.10, 2015 , pp. 4177-4183 More about this Journal
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
Gastric neoplasm; CD133; Lgr5; VM; MVD; CSCs;
Citations & Related Records
연도 인용수 순위
  • Reference
1 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.   DOI
2 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.   DOI
3 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.   DOI
4 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.   DOI
5 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.
6 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.   DOI
7 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.
8 Rosen JM, Jordan CT (2009). The increasing complexity of the cancer stem cell paradigm. Science, 324, 1670-3.   DOI
9 Sato T, Clevers H (2013). Growing self-organizing miniguts from a single intestinal stem cell, mechanism and applications. Science, 340, 1190-4.   DOI
10 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.   DOI
11 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.   DOI
12 Shirakawa K, Wakasugi H, Heike Y, et al (2002). Vasculogenic mimicry and pseudo-comedo formation in breast cancer. Int J Cancer, 99, 821-8.   DOI
13 Singh SK, Hawkins C, Clarke ID, et al (2004). Identification of human brain tumour initiating cells. Nature, 432, 396-401.   DOI
14 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.   DOI
15 Sun B, Qie S, Zhang S, et al (2008). Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors. Hum Pathol, 39, 445-51.
16 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.
17 Sun D, Sun B, Liu T, et al (2013). Slug promoted vasculogenic mimicry in hepatocellular carcinoma. J Cell Mol Med, 17, 1038-47.   DOI
18 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.   DOI
19 Tang HS, Feng YJ, Yao LQ (2009). Angiogenesis, vasculogenesis, and vasculogenic mimicry in ovarian cancer. Int J Gynecol Cancer, 19, 605-10.   DOI
20 Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65, 87-108.   DOI
21 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.
22 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.   DOI
23 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.   DOI
24 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.   DOI
25 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.   DOI
26 Yang L, Levi E, Zhu S, Du J, Majumdar AP (2013). Cancer stem cells biomarkers in gastric carcinogenesis. J Gastrointest Cancer, 44, 428-35.   DOI
27 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.   DOI
28 Yin AH, Miraglia S, Zanjani ED, et al (1997). AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood, 90, 5002-12.
29 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.   DOI
30 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.   DOI
31 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.
32 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.   DOI
33 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.   DOI
34 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.   DOI
35 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.
36 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.   DOI
37 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.   DOI   ScienceOn
38 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.
39 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.
40 EI Hallani S, Boisselier B, Peglion F, et al (2010). A new alternative mechanism in glioblastoma vascularization, tubular vasculogenic mimicry. Brain, 133, 973-982.   DOI
41 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.   DOI
42 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.   DOI
43 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.   DOI
44 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.   DOI
45 Hendrix MJ, Seftor EA, Hess AR, Seftor RE (2003). Vasculogenic mimicry and tumour-cell plasticity, lessons from melanoma. Nat Rev Cancer, 3, 411-21.   DOI
46 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.   DOI
47 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.   DOI
48 Huang J, Chen K, Gong W, Dunlop NM, Wang JM (2008). G-protein coupled chemoattractant receptors and cancer. Front Biosci, 13, 3352-63.
49 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.   DOI
50 Li M, Gu Y, Zhang Z, et al (2010). Vasculogenic mimicry, a new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res, 16, 259-66.   DOI
51 Lin KK, Andersen B (2008). Have hair follicle stem cells shed their tranquil image? Cell Stem Cell, 3, 581-2.   DOI
52 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.   DOI
53 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.   DOI
54 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].