|Table of Contents|

ALDH1A1 enhances the expression of angiogenesis factor in breast cancer cells and promotes tubule formation and invasion of co-cultured HUVEC cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2021 04
Page:
552-559
Research Field:
Publishing date:

Info

Title:
ALDH1A1 enhances the expression of angiogenesis factor in breast cancer cells and promotes tubule formation and invasion of co-cultured HUVEC cells
Author(s):
ZHAO Hongyu; Abduhini·Tursun; FAN Mingjiang
Surgical Oncology of Breast and Thyroid,the First People's Hospital of Kashgar,Xinjiang Kashgar 844000,China.
Keywords:
breast cancer; aldehyde dehydrogenase 1A1; retinoic acid; hypoxia inducible factor-1α; invasion; angiogenesis
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2021.04.003
Abstract:
Objective：To investigate the effect of stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) on the expression of angiogenic factors in breast cancer cells and the effect of tubule formation and invasion on HUVEC cells co-cultured with breast cancer cells.Methods:The expression of ALDH1A1 in breast cancer tissues and breast hyperplasia tissues was detected by immunohistochemistry.Breast cancer cells (MCF-7 and MDA-MB-231) were transfected with ALDH1A1 shRNA or overexpressing ALDH1A1-pcDNA3.1 plasmid,and the effects of knockdown or overexpression of ALDH1A1 on the expression of vascular endothelial growth factor (VEGF),hypoxia inducible factor-1α (HIF-1α) and interleukin-12 (IL-12) in breast cancer cells were detected by qRT-PCR and Western blot.Breast cancer cells were treated with exogenous RA and RAR blocker (AGN 193109) for 48 hours to investigate whether retinoic acid signaling pathway was involved in the regulation of ALDH1A1 on VEGF and HIF-1α.Breast cancer cells (MCF-7 and MDA-MB-231) and HUVEC cells were co-cultured to mimic the microenvironment of tumor formation,and the tubular formation ability and cell invasion ability of HUVEC were examined.Results:The mean optical density of ALDH1A1 staining in breast cancer tissues was significantly higher than that in breast hyperplasia tissues,and the lymph node metastasis of breast cancer tissues was significantly higher than that in non-lymph node metastatic breast cancer tissues (P＜0.05).Knockdown of ALDH1A1 significantly reduced VEGF and HIF-1α protein expression and up-regulated IL-12 protein expression in MCF-7 and MDA-MB-231 cells.However,up-regulation of ALDH1A1 expression reversed these changes.Exogenous RA treatment significantly up-regulated the expression of VEGF and HIF-1α in MCF-7 and MDA-MB-231 cells,however,RAR blocker treatment inhibited the up-regulation of VEGF and HIF-1α in MCF-7 and MDA-MB-231 cells.Knockdown of ALDH1A1 expression in breast cancer cells resulted in a significant decrease in tubule formation and invasive ability of co-cultured HUVEC cells.Up-regulation of ALDH1A1 expression in breast cancer cells significantly promoted tubule formation and invasion of co-cultured HUVEC cells.Conclusion:In breast cancer cells,ALDH1A1 up-regulates the expression of angiogenic factors and increases the angiogenic capacity of co-cultured endothelial cells by activating HIF-1α and retinoic acid signaling pathways,thereby increasing tumor invasiveness.

References:

［1］ RONCA R,BENKHEIL M,MITOLA S,et al.Tumor angiogenesis revisited:Regulators and clinical implications［J］.Medicinal Research Reviews,2017,37(6):1231-1274.
[2] 张新明,郭德迎,何海填,等.肿瘤相关巨噬细胞对膀胱癌细胞增殖和血管生成的影响［J］.现代肿瘤医学,2018,26(24):3908-3911. ZHANG XM,GUO DY,HE HT,et al.The effect of tumor associated macrophages on angiogenesis and proliferation of bladder cancer cells［J］.Modern Oncology,2018,26(24):3908-3911.
[3] FESSLER E,DIJKGRAAF FE,FELIPE DSEM,et al.Cancer stem cell dynamics in tumor progression and metastasis:Is the microenvironment to blame［J］.Cancer Letters,2013,341(1):97-104.
[4] VISSAPRAGADA R,CONTRERAS MA,DA SILVA CG,et al.Bidirectional crosstalk between periventricular endothelial cells and neural progenitor cells promotes the formation of a neurovascular unit［J］.Brain Research,2014,1565:8-17.
[5] XIE TX,XIA Z,ZHANG N,et al.Constitutive NF-kappaB activity regulates the expression of VEGF and IL-8 and tumor angiogenesis of human glioblastoma［J］.Oncology Reports,2010,23(3):725-732.
[6] CHARAFE-JAUFFRET E,GINESTIER C,IOVINO F,et al.Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer［J］.Clinical Cancer Research,2010,16(1):45-55.
[7] 毛俊,张晴晴,李连宏,等.乳腺癌组织中EGF和ALDH1A1的表达及其临床意义［J］.山东医药,2012,52(32):1-3. MAO J,ZHANG QQ,LI LH,et al.Expression and significance of EGF and ALDH1A1 in breast cancer［J］.Shandong Medical Journal,2012,52(32):1-3.
[8] LEID M,KASTNER P,CHAMBON P.Multiplicity generates diversity in the retinoic acid signalling pathways［J］.Trends in Biochemical Sciences,1992,17(10):427-433.
[9] MARCATO P,DEAN CA,LIU RZ,et al.Aldehyde dehydrogenase 1A3 influences breast cancer progression via differential retinoic acid signaling［J］.Molecular Oncology,2015,9(1):17-31.
[10] GUIDI AJ,SCHNITT SJ,FISCHER L,et al.Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast［J］.Cancer,1997,80(10):1945-1953.
[11] MCMAHON G.VEGF receptor signaling in tumor angiogenesis［J］.Oncologist,2000,5 Suppl 1(Suppl 1):3-10.
[12] 于德新,高志芹.肿瘤血管生长抑制因子与肝细胞癌关系研究进展［J］.中华肿瘤防治杂志,2005,12(17):1350-1354. YU DX,GAO ZQ.Advances in correlation of angioinhibitory factors and hepatocellular carcinoma［J］.Chinese Journal of Cancer Prevention and Treatment,2005,12(17):1350-1354.
[13] TOMITA H,TANAKA K,TANAKA T,et al.Aldehyde dehydrogenase 1A1 in stem cells and cancer［J］.Oncotarget,2016,7(10):11018-11032.
[14] PLAKS V,KONG N,WERB Z.The cancer stem cell niche:How essential is the niche in regulating stemness of tumor cells［J］.Cell Stem Cell,2015,16(3):225-238.
[15] ADORNO-CRUZ V,KIBRIA G,LIU X,et al.Cancer stem cells:Targeting the roots of cancer,seeds of metastasis,and sources of therapy resistance［J］.Cancer Research,2015,75(6):924-929.
[16] LAGORY EL,GIACCIA AJ.The ever-expanding role of HIF in tumour and stromal biology［J］.Nature Cell Biology,2016,18(4):356.
[17] NAGARAJAN S,SELVARAJ P.Glycolipid-anchored IL-12 expressed on tumor cell surface induces antitumor immune response［J］.Cancer Research,2002,62(10):2869-2874.
[18] KALITIN NN,KARAMYSHEVA AF.RARα mediates all-trans-retinoic acid-induced VEGF-C,VEGF-D and VEGFR3 expression in lung cancer cells［J］.Cell Biology International,2016,40(4):456-464.
[19] 刘龙阳,姚婷婷,易娟娟,等.干扰ALDH1A1表达的shRNA载体成功转染宫颈癌HeLa细胞及意义［J］.国际妇产科学杂志,2013,40(2):176-178. LIU LY,YAO TT,YI JJ,et al.The success and significance of shRNA of ALDH1A1 gene transfection to hela cell lines［J］.Journal of International Obstetrics and Gynecology,2013,40(2):176-178.
[20] MIERKE CT.Cancer cells regulate biomechanical properties of human microvascular endothelial cells［J］.Journal of Biological Chemistry,2011,286(46):40025-40037.
[21] SJSTRM M,HARTMAN L,HONETH G,et al.Stem cell biomarker ALDH1A1 in breast cancer shows an association with prognosis and clinicopathological variables that is highly cut-off dependent［J］.J Clin Pathol,2015,68(12):1012-1019.

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新疆维吾尔族自治区科技支疆项目（编号：2017E0263）
Last Update: 1900-01-01