Overexpression of Annexin A1 is associated with the formation of capillaries in infantile hemangioma

Pan,Xinyuan; Hui,Huang; Teng,Xiaopin; Wei,Kuicheng

doi:10.3892/mco.2022.2566

Overexpression of Annexin A1 is associated with the formation of capillaries in infantile hemangioma

Authors:
- Xinyuan Pan
- Huang Hui
- Xiaopin Teng
- Kuicheng Wei
View Affiliations

Affiliations: Department of Plastic Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China, Department of Orthopedics, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530001, P.R. China
Published online on: July 12, 2022 https://doi.org/10.3892/mco.2022.2566
Article Number: 133
Copyright: © Pan 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

Infantile hemangioma is a common benign tumor in infants. However, the molecular mechanism that controls the proliferation and differentiation of hemangioma is not well understood. Annexin A1 (ANX A1) is a phospholipid‑binding protein involved in a variety of biological processes, including inflammation, cell proliferation and apoptosis. To explore the significance of ANX A1 in the process of proliferation or differentiation of hemangioma, proliferating and involuting hemangioma tissues were collected to detect the expression of ANX A1 using immunohistochemistry and western blotting. Normal skin tissues were used as the negative control. The results revealed that ANX A1 was upregulated in the proliferative phase of hemangioma, and its expression was decreased when the hemangioma entered the involuting phase. Additionally, in the proliferative phase, the strongest staining of ANX A1 was observed in newly born capillaries, and the staining of ANX A1 became weaker in enlarged vessels, indicating that ANX A1 plays an important role in promoting the formation of capillaries. The expression of hypoxia‑inducible factor (HIF)‑1α was positively associated with the expression trend of ANX A1, suggesting that the overexpression of ANX A1 may be associated with the increase of HIF‑1α. In summary, the results of the present study revealed that the expression of ANX A1 was increased in proliferating hemangioma tissue, and that high expression of ANX A1 may be closely associated with the formation of capillaries in infantile hemangioma.

View Figures

View References

1	Kanada KN, Merin MR, Munden A and Friedlander SF: A prospective study of cutaneous fifindings in newborns in the United States: Correlation with race, ethnicity, and gestational status using updated classifification and nomenclature. J Pediatr. 161:240–245. 2012.PubMed/NCBI View Article : Google Scholar
2	Kilcline C and Frieden IJ: Infantile hemangiomas: How common are they? A systematic review of the medical literature. Pediatr Dermatol. 25:168–173. 2008.PubMed/NCBI View Article : Google Scholar
3	Couto RA, Maclellan RA, Zurakowski D and Greene AK: Infantile hemangioma: Clinical assessment of the involuting phase and implications for management. Plast Reconstr Surg. 130:619–624. 2012.PubMed/NCBI View Article : Google Scholar
4	Nguyen HP, Pickrell BB and Wright TS: Beta-blockers as therapy for infantile hemangiomas. Semin Plast Surg. 28:87–90. 2014.PubMed/NCBI View Article : Google Scholar
5	Priya C, Varshini C and Biswakumar B: Case report: A rare case of infantile hemangioma, treated in a private clinic as out patient. Prim Health Care. 9(321)2019.
6	Wu Y, Li H, Xie J, Wang F, Cao D and Lou Y: miR-139-5p affects cell proliferation, migration and adipogenesis by targeting insulin-like growth factor 1 receptor in hemangioma stem cells. Int J Mol Med. 45:569–577. 2020.PubMed/NCBI View Article : Google Scholar
7	Jin W, Chen L, Gao F, Yang M, Liu Y and Wang B: Down-regulation of miR-556-3p inhibits hemangioma cell proliferation and promotes apoptosis by targeting VEGFC. Cell Mol Biol (Noisy-le-grand). 66:204–207. 2020.PubMed/NCBI
8	Lim LH and Pervaiz S: Annexin 1: The new face of an old molecule. FASEB J. 21:968–975. 2007.PubMed/NCBI View Article : Google Scholar
9	Biaoxue R, Xiguang C and Shuanying Y: Annexin A1 in malignant tumors: Current opinions and controversies. Int J Biol Markers. 29:e8–e20. 2014.PubMed/NCBI View Article : Google Scholar
10	Rubinstein MR, Baik JE, Lagana SM, Han RP, Raab WJ, Sahoo D, Dalerba P, Wang TC and Han YW: Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β-catenin modulator Annexin A1. EMBO Rep. 20(e47638)2019.PubMed/NCBI View Article : Google Scholar
11	Boudhraa Z, Rondepierre F, Ouchchane L, Kintossou R, Trzeciakiewicz A, Franck F, Kanitakis J, Labeille B, Joubert-Zakeyh J, Bouchon B, et al: Annexin A1 in primary tumors promotes melanoma dissemination. Clin Exp Metastasis. 31:749–760. 2014.PubMed/NCBI View Article : Google Scholar
12	Pessolano E, Belvedere R, Bizzarro V, Franco P, Marco I, Porta A, Tosco A, Parente L, Perretti M and Petrella A: Annexin A1 may induce pancreatic cancer progression as a key player of extracellular vesicles effects as evidenced in the in vitro MIA PaCa-2 model system. Int J Mol Sci. 19(3878)2018.PubMed/NCBI View Article : Google Scholar
13	Lin Y, Lin G, Fang W, Zhu H and Chu K: Increased expression of annexin A1 predicts poor prognosis in human hepatocellular carcinoma and enhances cell malignant phenotype. Med Oncol. 31(327)2014.PubMed/NCBI View Article : Google Scholar
14	Paweletz CP, Ornstein DK, Roth MJ, Bichsel VE, Gillespie JW, Calvert VS, Vocke CD, Hewitt SM, Duray PH, Herring J, et al: Loss of annexin 1 correlates with early onset of tumorigenesis in esophageal and prostate carcinoma. Cancer Res. 60:6293–6297. 2000.PubMed/NCBI
15	Zhu DW, Yang X, Yang CZ, Ma J, Liu Y, Yan M, Wang LZ, Li J, Zhang CP, Zhang ZY and Zhong LP: Annexin A1 down-regulation in oral squamous cell carcinoma correlates to pathological differentiation grade. Oral Oncol. 49:542–550. 2013.PubMed/NCBI View Article : Google Scholar
16	Ge Y, Li S, Hu XY, Tong HL, Li SF and Yan YQ: TCEA3 promotes differentiation of C2C12 cells via an Annexin A1-mediated transforming growth factor-β signaling pathway. J Cell Physiol. 234:10554–10565. 2019.PubMed/NCBI View Article : Google Scholar
17	Vishwanatha JK, Salazar E and Gopalakrishnan VK: Absence of annexin I expression in B-cell non-Hodgkin's lymphomas and cell lines. BMC Cancer. 4(8)2004.PubMed/NCBI View Article : Google Scholar
18	de Jong S, Itinteang T, Withers AH, Davis PF and Tan ST: Does hypoxia play a role in infantile hemangioma? Arch Dermatol Res. 308:219–227. 2016.PubMed/NCBI View Article : Google Scholar
19	Adams JM, Difazio LT, Rolandelli RH, Luján JJ, Haskó G, Csóka B, Selmeczy Z and Németh ZH: HIF-1: A key mediator in hypoxia. Acta Physiol Hung. 96:19–28. 2009.PubMed/NCBI View Article : Google Scholar
20	Marchuk DA: Pathogenesis of hemangioma. J Clin Invest. 107:665–666. 2001.PubMed/NCBI View Article : Google Scholar
21	Aydin Köker S, Kömüroğlu AU, Köksoy AY, Şiraz ÜG, Tekin E and Köker A: Evaluation of GLUT1, IGF-2, VEGF, FGF 1, and angiopoietin 2 in infantile hemangioma. Arch Pediatr. 28:296–300. 2021.PubMed/NCBI View Article : Google Scholar
22	Yin RR, Hao D and Chen P: Expression and correlation of MMP-9, VEGF, and p16 in infantile hemangioma. Eur Rev Med Pharmacol Sci. 22:4806–4811. 2018.PubMed/NCBI View Article : Google Scholar
23	Thaivalappil S, Bauman N, Saieg A, Movius E, Brown KJ and Preciado D: Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas. JAMA Otolaryngol Head Neck Surg. 139:1026–1031. 2013.PubMed/NCBI View Article : Google Scholar
24	Şen HS, Yalçın B, Canpınar H, Ocak S and Akyüz C: Serum levels of VEGF and bFGF in infantile hemangiomas treated with propranolol. Turk J Pediatr. 62:979–985. 2020.PubMed/NCBI View Article : Google Scholar
25	Park M, Jung HL, Shim YJ, Kim HS, Yoon HS, Park SK, Cheuh HW, Lee MJ, Lee JM, Park ES, et al: Serum cytokine profiles in infants with infantile hemangiomas on oral propranolol treatment: VEGF and bFGF, potential biomarkers predicting clinical outcomes. Pediatr Res. 88:749–755. 2020.PubMed/NCBI View Article : Google Scholar
26	Rotter A, Lima XT and Oliveira ZNP: Evaluation of plasma and urinary levels of vascular endothelial growth factor and matrix metalloproteinase-9 in patients with infantile hemangioma. Int J Dermatol. 60:1263–1269. 2021.PubMed/NCBI View Article : Google Scholar
27	Lacerda JZ, Drewes CC, Mimura KKO, Zanon CF, Ansari T, Gil CD, Greco KV, Farsky SHP and Oliani SM: Annexin A1_2-26 treatment improves skin heterologous transplantation by modulating inflammation and angiogenesis processes. Front Pharmacol. 9(1015)2018.PubMed/NCBI View Article : Google Scholar
28	Yi M and Schnitzer JE: Impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1-null mice. Proc Natl Acad Sci USA. 106:17886–17891. 2009.PubMed/NCBI View Article : Google Scholar
29	Ramakrishnan S, Anand V and Roy S: Vascular endothelial growth factor signaling in hypoxia and inflammation. J Neuroimmune Pharmacol. 9:142–160. 2014.PubMed/NCBI View Article : Google Scholar
30	Wang X, Tang G and Sun H: Effect of hypoxia on the proliferation and expressions of hypoxia-inducible factor-1α, vascular endothelial growth factor and matrix metalloproteinase-9 in keratinocytes obtained from oral lichen planus lesions. Zhonghua Kou Qiang Yi Xue Za Zhi. 50:89–94. 2015.PubMed/NCBI(In Chinese).
31	Liao SH, Zhao XY, Han YH, Zhang J, Wang LS, Xia L, Zhao KW, Zheng Y, Guo M and Chen GQ: Proteomics-based identification of two novel direct targets of hypoxia-inducible factor-1 and their potential roles in migration/invasion of cancer cells. Proteomics. 9:3901–3912. 2009.PubMed/NCBI View Article : Google Scholar
32	Yang F, Cai J, Zhan H, Situ J, Li W, Mao Y and Luo Y: Suppression of TRPM7 inhibited hypoxia-induced migration and invasion of androgen-independent prostate cancer cells by enhancing RACK1-mediated degradation of HIF-1α. Oxid Med Cell Longev. 2020(6724810)2020.PubMed/NCBI View Article : Google Scholar
33	Roskoski R Jr: ERK1/2 MAP kinases: Structure, function, and regulation. Pharmacol Res. 66:105–143. 2012.PubMed/NCBI View Article : Google Scholar
34	Lee CC, Chen SC, Tsai SC, Wang BW, Liu YC, Lee HM and Shyu KG: Hyperbaric oxygen induces VEGF expression through ERK, JNK and c-Jun/AP-1 activation in human umbilical vein endothelial cells. J Biomed Sci. 13:143–156. 2006.PubMed/NCBI View Article : Google Scholar
35	Catar R, Moll G, Hosp I, Simon M, Luecht C, Zhao H, Wu D, Chen L, Kamhieh-Milz J, Korybalska K, et al: Transcriptional regulation of thrombin-induced endothelial VEGF induction and proangiogenic response. Cells. 10(910)2021.PubMed/NCBI View Article : Google Scholar
36	Poeter M, Radke S, Koese M, Hessner F, Hegemann A, Musiol A, Gerke V, Grewal T and Rescher U: Disruption of the annexin A1/S100A11 complex increases the migration and clonogenic growth by dysregulating epithelial growth factor (EGF) signaling. Biochim Biophys Acta. 1833:1700–1711. 2013.PubMed/NCBI View Article : Google Scholar
37	Pin AL, Houle F, Fournier P, Guillonneau M, Paquet ÉR, Simard MJ, Royal I and Huot J: Annexin-1-mediated endothelial cell migration and angiogenesis are regulated by vascular endothelial growth factor (VEGF)-induced inhibition of miR-196a expression. J Biol Chem. 287:30541–30551. 2012.PubMed/NCBI View Article : Google Scholar
38	Wei L, Li L, Liu L, Yu R, Li X and Luo Z: Knockdown of Annexin-A1 Inhibits growth, migration and invasion of glioma cells by suppressing the PI3K/Akt signaling pathway. ASN Neuro. 13(17590914211001218)2021.PubMed/NCBI View Article : Google Scholar
39	Minet E, Arnould T, Michel G, Roland I, Mottet D, Raes M, Remacle J and Michiels C: ERK activation upon hypoxia: Involvement in HIF-1 activation. FEBS Lett. 468:53–58. 2000.PubMed/NCBI View Article : Google Scholar
40	Liu L, Ning X, Han S, Zhang H, Sun L, Shi Y, Sun S, Guo C, Yin F, Qiao T, et al: Hypoxia induced HIF-1 accumulation and VEGF expression in gastric epithelial mucosa cells: Involvement of ERK1/2 and PI3K/Akt. Mol Biol (Mosk). 42:459–469. 2008.PubMed/NCBI(In Russian).