|Table of Contents|

The mechanism of Tie-2 in the process of oral squamous cell carcinoma invading the jaw

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

Issue:
2023 13
Page:
2412-2417
Research Field:
Publishing date:

Info

Title:
The mechanism of Tie-2 in the process of oral squamous cell carcinoma invading the jaw
Author(s):
AI Mengsheng1SHEN Yang1GAO Mingyu1ZHANG Qinghua1FEI Wei12
1.School of Stomatology,Southwest Medical University,Sichuan Luzhou 646000,China;2.Department of Stomatology,Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital,Sichuan Chengdu 610072,China.
Keywords:
oral squamous cell carcinomaTie-2osteoclastsbone invasion
PACS:
R739.8
DOI:
10.3969/j.issn.1672-4992.2023.13.008
Abstract:
Objective:To study the mechanism of Tie-2(tyrosinekinase receptor-2) in the process of oral squamous cell carcinoma invading the jaw.Methods:Immunohistochemistry was used to compare the expression of Tie-2 in oral squamous cell carcinoma at the front of jaw invasion and other oral squamous cell carcinoma.Three siRNA lentiviral vectors(662,663,664) against Tie-2 were constructed as the experimental group,no-load virus 429 and normal saline(NS) as the control group,and each group was transfected into the hunan tongue squamous carcinoma cell line(Cal-27),the siRNA with the best inhibitory effect was screened by qRT-PCR.The cell viability was detected by CCK-8 method.The lentiviral vector with the best inhibitory effect was transfected into Cal-27,the culture supernatant was added to the human monocytic cell line(THP-1) medium,the expression of mRNA and protein in osteoclast function related genes TRAP(tartrate resistant acid phosphatase) and CTSL(cathepsin K) in THP-1 were detected by qRT-PCR and Western blotting.Results:The staining of the parosteal OSCC tissue at the invasion edge of the jaw was significantly deeper than that at other parts of the OSCC tissue,and the MOD value of parosteal OSCC tissue was significantly increased(P<0.000 1).siRNA-664 had the best inhibitory effect on the expression of Tie-2 in Cal-27.After transfecting Cal-27 and THP-1 with lentivirus,the cell viability did not change significantly,and the difference was not statistically significant.After silencing the expression of Tie-2 in Cal-27,theosteoclast function-related genes and proteins of THP-1 significantly reduced expression.Conclusion:After down-regulating the expression of Tie-2,the potential of THP-1 to differentiate into osteoclasts was reduced,which is manifested as the down-regulation of osteoclast function-related genes and proteins.OSCC may release some osteoclast differentiation factors by activating the Ang/Tie-2 signaling system to promote osteoclast differentiation,thereby leading to local bone invasion.

References:

[1]GOU L,YANG W,QIAO X,et al.Marginal or segmental mandibulectomy:treatment modality selection for oral cancer:a systematic review and meta-analysis[J].Int J Oral Maxillofac Surg,2018,47(1):1-10.
[2]PINK R,MICHALEK J,KRAL D,et al.Importance of evaluation of bone invasion type in squamous cell carcinomas of the oral cavity and oropharynx[J].Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2021,55(7):62-67.
[3]SPROLL CK,HOLTMANN H,SCHORN LK,et al.Mandible handling in the surgical treatment of oral squamous cell carcinoma:lessons from clinical results after marginal and segmental mandibulectomy[J].Oral Surg Oral Med Oral Pathol Oral Radiol,2020,129(6):556-564.
[4]GUISE TA,MUNDY GR.Cancer and bone[J].Endocr Rev,1998,19(1):18-54.
[5]JIMI E,FURUTA H,MATSUO K,et al.The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma[J].Oral Dis,2011,17(5):462-468.
[6]ALI ZA,RINZE R,DOUGLAS G,et al.Tetrahydrobiopterin determinesvascular remodeling through enhanced endothelial cell survival and regeneration[J].Circulation,2013,128(11):50-58.
[7]PIROUZPANAH S,VARSHOSAZ P,FAKHRJOU A,et al.The contribution of dietary and plasma folate and cobalamin to levels of angiopoietin-1,angiopoietin-2 and Tie-2 receptors depend on vascular endothelial growth f-actor status of primary breast cancer patients[J].Sci Rep,2019,9(1):51-63.
[8]ARAI F,HIRAO A,OHMURA M,et al.Tie-2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche[J].Cell,2004,118(2):149-161.
[9]CHEN Y,DONNELLY E,KOBAYASHI H,et al.Gene therapy targeting the Tie-2 function ameliorates collagen-induced arthritis and protects against bone destruction[J].Arthritis Rheum,2019,52(5):1585-1594.
[10]MIN Y,REN X,VAUGHT DB,et al.Tie-2 signaling regulates osteoclastogenesis and osteolytic bone invasion of breast cancer[J].Cancer Res,2010,70(7):2819-2828.
[11]NAKAMURA M,AOYAMA N,YAMAGUCHI S,et al.Expression of tartrate-resistant acid phosphatase and cathepsin K during osteoclast differentiation in developing mouse mandibles[J].Biomed Res,2021,42(1):13-21.
[12]YAMASHITA K,IWATAKE M,OKAMOTO K,et al.Cathepsin K modulates invasion,migration and adhesion of oral squamous cell carcinomas in vitro[J].Oral Dis,2017,23(4):518-525.
[13]KARAGIANNIS GS,PASTORIZA JM,WANG Y,et al.Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism[J].Sci Transl Med,2017,9(397):26-35.
[14]SINGH A,MAIR M,SINGHVI H,et al.Incidence,predictors and impact of positive bony margins in surgically treated T4 stage cancers of the oral cavity[J].Oral Oncol,2019,9(1):8-12.
[15]MICHALEK J,BRYCHTOVA S,PINK R,DVORAK Z.Prognostic and predictive markers for perineural and bone invasion of oral squamous cell carcinoma[J].Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub,2019,163(4):302-308.
[16]AHMAD JG,NAMIN AW,JORGENSEN JB,et al.Mandibular invasion by oral squamous cell carcinoma:Clinicopathologic features of 74 cases[J].Otolaryngol Head Neck Surg,2019,160(6):1034-1041.
[17]SHAN Q,TAKABATAKE K,KAWAI H,et al.Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes[J].Oncol Rep,2022,47(4):81-83.
[18]SONSH,PARK J,JUNG MJ,et al.Transforming growth factor-β-regulated fractalkine as a marker of erosive bone invasion in oral squamous cell carcinoma[J].Eur J Oral Sci,2021,129(1):750-758.
[19]TADA T,SHIN M,FUKUSHIMA H,et al.Oral squamous cell carcinoma cells modulate osteoclast function by RANKL-dependent and-independent mechanisms[J].Cancer Lett,2009,274(1):126-131.
[20]UDAGAWA N,KOIDE M,NAKAMURA M,et al.Osteoclast differentiation by RANKL and OPG signaling pathways[J].Bone Miner Metab,2021,39(1):19-26.
[21]GYORI DS,MOCSAI A.Osteoclast signal transduction during bone metastasis formation[J].Front Cell Dev Biol,2020,8(4):507-522.
[22]YU JUNGEUN,ERNESTO CANALIS.Notch and the regulation of osteoclast differentiation and function[J].Bone,2020,12(8):474-508.

Memo

Memo:
四川省科技计划项目(编号:2017JY0082);四川省人民医院院基金重点项目(编号:2021LZ01)
Last Update: 2023-05-31