Tumor angiogenesis is the tumor’s inherent blood supply system which is crucial for the growth of tumor. Extracellular Matrix Metallo Proteinases Inducer (EMMPRIN)/Cluster of Differentiation 147 (CD147) is found in high levels on tumor surfaces. This study focuses on these elevated levels of CD147 and the effect it has on tumor angiogenesis. The present article develops a Two-Dimensional Mathematical Model of Tumor Angiogenesis taking into account the CD147 molecule. The effects of CD147 on Tumor Angiogenesis Factors (TAFs), fibronectin and Matrix Metallo Proteinases (MMPs) are also incorporated. The results have been obtained through COMSOL Multiphysics 5.4 software. The results show that CD147 is responsible for swifter angiogenesis, calling for targeting this molecule in anti-angiogenic strategies. The present model is validated with the existing theoretical and experimental results.
LeeSYJuMKJeonHM, et al. Regulation of tumor progression by programmed necrosis. Oxid Med Cell Longev2018; 2018:1–28.
4.
WangZZhaoZJiangT, et al. The multistep functions of EMMPRIN/ CD147 in the tumor angiogenesis. Cell Mol Med: Open access2016; 02(01): 12.
5.
TalmadgeJEFidlerIJ. AACR Centennial Series: the Biology of Cancer Metastasis: Historical Perspective. Cancer Res2010; 70(14): 5649–5669.
6.
ShweikiDNeemanMItinA, et al. Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: Implications for tumor angiogenesis. Proc Natl Acad Sci USA1995; 92:768–772.
7.
ShinJYYoonIHKimJS, et al. Vascular endothelial growth factor-induced chemotaxis and IL-10 from T cells. Cell Immunol2009; 256(1–2): 72–78.
8.
LuganoRRamachandranMDimbergA. Tumor angiogenesis: causes, consequences, challenges and opportunities, review. Cell Mol Life Sci2020; 77(9): 1745–1770.
9.
WalkerCMojaresEDel Río HernándezA. Role of extracellular matrix in development and cancer progression. Int J Mol Sci2018; 19(10): 3028.
10.
OudinMJJonasOKosciukT, et al. Tumor cell-driven extracellular matrix remodeling drives haptotaxis during metastatic progression. Cancer Discov2016; 6(5): 516–531.
11.
AcharyyaSMatrisianLWelchDR, et al. Invasion and metastasis, chapter 18. In: MendelsohnJGrayJ. W.HowleyP. M., et al. (eds) The molecular basis of cancer, 4th ed. W.B.Saunders, 2015, pp.269–284.e2.
12.
Stetler-StevensonWGHewittRCorcoranM. Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Semin Cancer Biol1996; 7(3): 147–154.
13.
XiongLEdwardsCk3rdZhouL. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int J Mol Sci2014; 15:17411–17441.
14.
BaiYHuangWMaLT, et al. Importance of N-glycosylation on CD147 for its biological functions. Int J Mol Sci2014; 15:6356–6377.
15.
HatanakaMHigashiYFukushigeT, et al. Cleaved CD147 shed from the surface of malignant melanoma cells activates MMP2 produced by fibroblasts. Anticancer Res2014; 34:7091–7096.
16.
WardJPKingJR. Mathematical modelling of avascular-tumour growth. IMA J Math Appl Med Biol1997; 14(1): 39–69.
17.
JiangYPjesivac-GrbovicJCantrellC, et al. A multiscale model for Avascular Tumor Growth. Biophys J2005; 89:3884–3894.
18.
MichelTFehrenbachJLobjoisV, et al. Mathematical Modeling of the proliferation gradient in MultiCellular tumor spheroids. J Theor Biol2018; 458:133–147.
19.
BaldingDMcElwainDL. A mathematical model of tumour-induced capillary growth. J Theor Biol1985; 114(1): 53–73.
20.
ChaplainMASleemanBD. A mathematical model for the production and secretion of tumour angiogenesis factor in tumours. IMA J Math Appl Med Biol1990; 7(2): 93–108.
21.
AndersonARChaplainMA. Continuous and discrete mathematical models of tumor-induced angiogenesis. Bull Math Biol1998; 60:857–899.
22.
AndersonARAChaplainMAJNewmanEL, et al. Mathematical modelling of tumour invasion and Metastasis. J Theor Med2000; 2:129–154.
23.
WeidleUHScheuerWEggleD, et al. Cancer-related issues of CD147, Review. Cancer Genomics Proteomics2010; 7:157–170.
24.
AbbasNFShabanaMEHabibFM, et al. Histopathological and immunohistochemical study of matrix metalloproteinase-2 and matrix metalloproteinase-9 in breast carcinoma. J Arab Soc Med Res2017; 12(1): 6–12.
25.
LiaoKLBaiXFFriedmanA. Mathematical Modeling of interleukin-35 promoting tumor growth and angiogenesis. PLoS One2014; 9(10): e110126.
26.
Wróbel-RoztropińskiAZielińska-KaźmierskaBRoztropińskiH, et al. Expression of matrix metalloproteinases (MMPs) and their inhibitor (TIMP) genes on mRNA and protein levels in oral squamous cell carcinoma, Nowotwory. J Oncol2021; 71(1): 1–8.
27.
Amit-CohenBCRahatMMRahatMA. Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN. Front Physiol2013; 4: 178.
28.
WieserSWeghuberJSamsM, et al. Cell-to-cell variability in the diffusion constants of the plasma membrane proteins CD59 and CD147. Soft Matter2009; 5:3287–3294.
29.
XiaoHWuR. Quantitative investigation of human cell surface N-glycoprotein dynamics. Chem Sci2017; 8:268–277.
30.
FranssenLCLorenziTBurgessAEF, et al. A mathematical framework for modelling the metastatic spread of cancer. Bull Math Biol2019; 81:1965–2010.
31.
CollierIELegantWMarmerB, et al. Diffusion of MMPs on the surface of collagen fibrils: the mobile cell surface-collagen substratum interface. PLoS One2011; 6(9): e24029.
32.
JiangCCuiCLiL, et al. The anomalous diffusion of a tumor invading with different surrounding tissues. PLoS One2014; 9(10): e109784.
33.
VoigtHVetter-KauczokCSSchramaD, et al. CD147 impacts angiogenesis and Metastasis Formation. Cancer Investig2009; 27(3): 329–333.
34.
XiongLDingLNingH, et al. CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells. Oncotarget2016; 7(36): 57737–57751.
35.
YuBZhangYWuK, et al. CD147 promotes progression of head and neck squamous cell carcinoma via NF-kappa B signaling. J Cell Mol Med2019; 23:954–966.
36.
SteuperaertMFalvo D’Urso LabateGDebbautC, et al. Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule. Drug Deliv2017; 24(1): 491–501.
37.
Rahimi-GorjiMVan de SandeLDebbautC, et al. Intraperitoneal aerosolized drug delivery: technology, recent developments, and future outlook. Adv Drug Deliv Rev2020; 160:105–114.
38.
Rahimi-GorjiMDebbautCWillaertW, et al. A numerical simulation of pressurized intraperitoneal aerosol chemotherapy (PIPAC): Validation Part. In: 18th National Day on Biomedical Engineering, Brussels, Belgium, 2019.
39.
GorjiMRDebbautCGhorbaniaslG, et al. Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC): finding the optimal electrical potential. Eur J Surg Oncol2021; 47:e30.
40.
Van de SandeLRahimi-GorjiMGiordanoS, et al. Electrostatic intraperitoneal aerosol delivery of nanoparticles: proof of concept and preclinical validation. Adv Healthc Mater2020; 9:2000655.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
