Association between ALDH1+/CD133+ stem-like cells and tumor angiogenesis in invasive ductal breast carcinoma

Lv,Xinquan; Wang,Yingzi; Song,Yimin; Pang,Xia; Li,Huixiang

doi:10.3892/ol.2016.4145

Association between ALDH1+/CD133+ stem-like cells and tumor angiogenesis in invasive ductal breast carcinoma

Authors:
- Xinquan Lv
- Yingzi Wang
- Yimin Song
- Xia Pang
- Huixiang Li
View Affiliations

Affiliations: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: January 26, 2016 https://doi.org/10.3892/ol.2016.4145
Pages: 1750-1756
Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The growth and metastasis of tumors is dependent on angiogenesis; however, the association between tumor stem cells (TSCs) and tumor angiogenesis remains to be elucidated. The present study aimed to investigate the expression of the TSC markers aldehyde dehydrogenase 1 (ALDH1) and cluster of differentiation 133 (CD133) in invasive ductal breast carcinoma, and identify their correlation with tumor angiogenesis. Stem‑like cells from the breast tissue of 120 patients, who were diagnosed with invasive ductal breast carcinoma at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, Henan, China) between January 2009 and December 2010, were collected by surgical resection and analyzed using immunohistochemical double staining. The expression of the vascular markers CD34, CD105 and vascular endothelial growth factor (VEGF) were determined using single staining. Overall, 25.83% (31/120) of the specimens contained a large number of ALDH1+/CD133+ stem‑like cells (ALDH1+/CD133+ tumor). ALDH1+/CD133+ expression is associated with microvessel density, VEGF‑positive rate and estrogen receptor expression (P<0.05); however, ALDH1+/CD133+ expression was not associated with age, tumor diameter, lymph node metastasis, histological classification, progesterone receptor expression or human epidermal growth factor receptor 2 expression (P>0.05). The ALDH1+/CD133+ tumor phenotype and expression of VEGF were identified to be correlated in the present study (P=0.020). The present study revealed a close association between breast cancer TSC markers, including ALDH1 and CD133, and tumor angiogenesis. The results of the present study may provide a novel target and treatment strategy for future studies investigating tumor growth and metastasis.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in: 2008 GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
2	Curado MP: Breast cancer in the world: Incidence and mortality. Salud Publica Mex. 53:372–384. 2011.PubMed/NCBI
3	Li CI, Anderson BO, Daling JR and Moe RE: Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA. 289:1421–1424. 2003. View Article : Google Scholar : PubMed/NCBI
4	Ernster VL, Barclay J, Kerlikowske K, Grady D and Henderson C: Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA. 275:913–918. 1996. View Article : Google Scholar : PubMed/NCBI
5	Lee S, Stewart S, Nagtegaal I, Luo J, Wu Y, Colditz G, Medina D and Allred DC: Differentially expressed genes regulating the progression of ductal carcinoma in situ to invasive breast cancer. Cancer Res. 72:4574–4586. 2012. View Article : Google Scholar : PubMed/NCBI
6	Wojnar A, Pula B, Piotrowska A, Jethon A, Kujawa K, Kobierzycki C, Rys J, Podhorska-Okolow M and Dziegiel P: Correlation of intensity of MT-I/II expression with Ki-67 and MCM-2 proteins in invasive ductal breast carcinoma. Anticancer Res. 31:3027–3033. 2011.PubMed/NCBI
7	Nanashima A, Hatachi G, Tsuchiya T, Matsumoto H, Arai J, Abo T, Murakami G, Tominaga T, Takagi K and Nagayasu T: Clinical significances of cancer stem cells markers in patients with intrahepatic cholangiocarcinoma who underwent hepatectomy. Anticancer Res. 33:2107–2114. 2013.PubMed/NCBI
8	Madjd Z, Ramezani B, Molanae S and Asadi-Lari M: High expression of stem cell marker ALDH1 is associated with reduced BRCA1 in invasive breast carcinomas. Asian Pac J Cancer Prev. 13:2973–2978. 2012. View Article : Google Scholar : PubMed/NCBI
9	Gil J, Stembalska A, Pesz KA and Sasiadek MM: Cancer stem cells: The theory and perspectives in cancer therapy. J Appl Genet. 49:193–199. 2008. View Article : Google Scholar : PubMed/NCBI
10	Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, et al: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 1:555–567. 2007. View Article : Google Scholar : PubMed/NCBI
11	Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C and Tabar V: Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 468:829–833. 2010. View Article : Google Scholar : PubMed/NCBI
12	O'Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007. View Article : Google Scholar : PubMed/NCBI
13	Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, Li ML, Tam KH, Lam CT, Poon RT and Fan ST: Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 47:919–928. 2008. View Article : Google Scholar : PubMed/NCBI
14	Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV and Varticovski L: Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res. 10:R102008. View Article : Google Scholar : PubMed/NCBI
15	Wu Y and Wu PY: CD133 as a marker for cancer stem cells: Progresses and concerns. Stem Cells Dev. 18:1127–1134. 2009. View Article : Google Scholar : PubMed/NCBI
16	Frierson HF Jr, Wolber RA, Berean KW, Franquemont DW, Gaffey MJ, Boyd JC and Wilbur DC: Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol. 103:195–198. 1995.PubMed/NCBI
17	Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P and Nakopoulou L: The clinicopathologic and prognostic significance of CD44+/CD24(−/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas. Human Pathol. 39:1096–1102. 2008. View Article : Google Scholar
18	Jasani B and Rhodes A: The role and mechanism of high-temperature antigen retrieval in diagnostic pathology. Curr Diag Pathol. 7:153–160. 2001. View Article : Google Scholar
19	Currie MJ, Beardsley BE, Harris GC, Gunningham SP, Dachs GU, Dijkstra B, Morrin HR, Wells JE and Robinson BA: Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: Relationships with markers of tumor hypoxia and microvascularity. Human Pathol. 44:402–411. 2013. View Article : Google Scholar
20	Shimizu M, Saitoh Y and Itoh H: Immunohistochemical staining of Ha-ras oncogene product in normal, benign, and malignant human pancreatic tissues. Hum Pathol. 21:607–612. 1990. View Article : Google Scholar : PubMed/NCBI
21	Moeller BJ, Cao Y, Li CY and Dewhirst MW: Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: Role of reoxygenation, free radicals, and stress granules. Cancer cell. 5:429–441. 2004. View Article : Google Scholar : PubMed/NCBI
22	Horbinski C, Mojesky C and Kyprianou N: Live free or die: Tales of homeless (cells) in cancer. Am J Pathol. 177:1044–1052. 2010. View Article : Google Scholar : PubMed/NCBI
23	Duffy JP, Eibl G, Reber HA and Hines OJ: Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer. Mol Cancer. 2:122003. View Article : Google Scholar : PubMed/NCBI
24	Wei B, Han XY, Qi CL, Zhang S, Zheng ZH, Huang Y, Chen TF and Wei HB: Coaction of spheroid-derived stem-like cells and endothelial progenitor cells promotes development of colon cancer. PloS One. 7:e390692012. View Article : Google Scholar : PubMed/NCBI
25	Martin TA and Jiang WG: Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma. Oncol Rep. 31:262–272. 2014.PubMed/NCBI
26	Platet N, Liu SY, Atifi ME, Oliver L, Vallette FM, Berger F and Wion D: Influence of oxygen tension on CD133 phenotype in human glioma cell cultures. Cancer Lett. 258:286–290. 2007. View Article : Google Scholar : PubMed/NCBI
27	Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, Shi Q, McLendon RE, Bigner DD and Rich JN: Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 66:7843–7848. 2006. View Article : Google Scholar : PubMed/NCBI
28	Panchision DM: The role of oxygen in regulating neural stem cells in development and disease. J Cell Physiol. 220:562–568. 2009. View Article : Google Scholar : PubMed/NCBI
29	Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD, Engh J, Iwama T, Kunisada T, Kassam AB, et al: Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1α. Oncogene. 28:3949–3959. 2009. View Article : Google Scholar : PubMed/NCBI
30	Ping YF, Yao XH, Jiang JY, Zhao LT, Yu SC, Jiang T, Lin MC, Chen JH, Wang B, Zhang R, et al: The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell-mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling. J Pathol. 224:344–354. 2011. View Article : Google Scholar : PubMed/NCBI
31	Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, et al: Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res. 71:3991–4001. 2011. View Article : Google Scholar : PubMed/NCBI
32	Fanelli M, Locopo N, Gattuso D and Gasparini G: Assessment of tumor vascularization: Immunohistochemical and non-invasive methods. Int J Biol Markers. 14:218–231. 1999.PubMed/NCBI
33	Pufe T, Harde V, Petersen W, Goldring MB, Tillmann B and Mentlein R: Vascular endothelial growth factor (VEGF) induces matrix metalloproteinase expression in immortalized chondrocytes. J Pathol. 202:367–374. 2004. View Article : Google Scholar : PubMed/NCBI
34	Takase Y, Kai K, Masuda M, Akashi M and Tokunaga O: Endoglin (CD105) expression and angiogenesis status in small cell lung cancer. Pathol Res Pract. 206:725–730. 2010. View Article : Google Scholar : PubMed/NCBI