Review

Research progress in the expression of versican in malignant tumors and its biological roles

  • LIU Linnan ,
  • FENG Li ,
  • WANG Long ,
  • LIU Jiayin ,
  • FAN Zhisong
Expand
  • Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
FAN Zhisong, E-mail: fanzs@hebmu.edu.cn.

Received date: 2023-10-09

  Accepted date: 2024-02-16

  Online published: 2024-04-28

Supported by

Natural Science Foundation of Hebei Province(H2022206523)

Abstract

Malignant tumors pose a serious threat to human health and are one of the main causes of human death worldwide. In order to further improve the therapeutic outcomes of malignant tumors and prolong patients' survival time, clarifying the pathogenesis of malignant tumors and searching for new diagnostic and therapeutic targets become particularly important. It has been found that the occurrence and development of malignant tumors are the results of the interaction between tumor cells and the tumor microenvironment (TME). Versican, encoded by the VCAN gene, is a type of chondroitin sulfate proteoglycan belonging to the exogenous lectin proteoglycan family. It is a major component of the extracellular matrix and plays an important role in embryonic development and inflammatory responses. As an important component of TME, versican is abnormally expressed in various tumor tissues such as renal cell carcinoma, hepatocellular carcinoma, and gastric cancer, and is closely related to the clinical pathological characteristics and prognosis of the patients. It is a potential biomarker for early diagnosis and prognostic evaluation of tumors. Further researches have shown that versican can promote tumor development in a number of ways, such as promoting tumor cell proliferation, invasion and metastasis, inhibiting tumor cell apoptosis, promoting tumor angiogenesis, and inhibiting anti-tumor immune responses. This article reviews the current research status of the expression and biological effects of versican in malignant tumors, aiming to provide reference for subsequent research, clinical diagnosis and treatment of tumors.

Cite this article

LIU Linnan , FENG Li , WANG Long , LIU Jiayin , FAN Zhisong . Research progress in the expression of versican in malignant tumors and its biological roles[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024 , 44(4) : 525 -530 . DOI: 10.3969/j.issn.1674-8115.2024.04.014

References

1 ISLAMI F, WARD E M, SUNG H, et al. Annual report to the nation on the status of cancer, part 1: national cancer statistics[J]. J Natl Cancer Inst, 2021, 113(12): 1648-1669.
2 CHEVRIER S, LEVINE J H, ZANOTELLI V R T, et al. An immune atlas of clear cell renal cell carcinoma[J]. Cell, 2017, 169(4): 736-749.e18.
3 KARAGIORGOU Z, FOUNTAS P N, MANOU D, et al. Proteoglycans determine the dynamic landscape of EMT and cancer cell stemness[J]. Cancers, 2022, 14(21): 5328.
4 KESH K, GUPTA V K, DURDEN B, et al. Therapy resistance, cancer stem cells and ECM in cancer: the matrix reloaded[J]. Cancers, 2020, 12(10): 3067.
5 HIRANI P, GAUTHIER V, ALLEN C E, et al. Targeting versican as a potential immunotherapeutic strategy in the treatment of cancer[J]. Front Oncol, 2021, 11: 712807.
6 MITSUI Y, SHIINA H, KATO T, et al. Versican promotes tumor progression, metastasis and predicts poor prognosis in renal carcinoma[J]. Mol Cancer Res, 2017, 15(7): 884-895.
7 吕磊, 郑福鑫, 周高峰, 等. 多功能蛋白聚糖基因对膀胱尿路上皮癌免疫浸润及预后的影响[J]. 解放军医学杂志, 2023, 48(8): 921-928.
7 Lü L, ZHENG F X, ZHOU G F, et al. Effect of VCAN on immune infiltration and prognosis of bladder urothelial carcinoma[J]. Medical Journal of Chinese People's Liberation Army, 2023, 48(8): 921-928.
8 SUN G S, ZHENG W B, TAN P Y, et al. Comprehensive analysis of VCAN expression profiles and prognostic values in HCC[J]. Front Genet, 2022, 13: 900306.
9 KATO K, FUKAI M, HATANAKA K C, et al. Versican secreted by cancer-associated fibroblasts is a poor prognostic factor in hepatocellular carcinoma[J]. Ann Surg Oncol, 2022, 29(11): 7135-7146.
10 WANG M Q, LI Y P, XU M, et al. VCAN, expressed highly in hepatitis B virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors[J]. World J Gastrointest Oncol, 2022, 14(10): 1933-1948.
11 DE WIT M, CARVALHO B, DELIS-VAN DIEMEN P M, et al. Lumican and versican protein expression are associated with colorectal adenoma-to-carcinoma progression[J]. PLoS One, 2017, 12(5): e0174768.
12 GUO J, LIU Y. INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN[J]. J Int Med Res, 2021, 49(6): 3000605211014998.
13 WANG L, FENG L, LIU L N, et al. Joint effect of THBS2 and VCAN accelerating the poor prognosis of gastric cancer[J]. Aging, 2023, 15(5): 1343-1357.
14 SONG J Q, WEI R Y, HUO S Y, et al. Versican enrichment predicts poor prognosis and response to adjuvant therapy and immunotherapy in gastric cancer[J]. Front Immunol, 2022, 13: 960570.
15 ZHAI L L, CHEN W J, CUI B S, et al. Overexpressed versican promoted cell multiplication, migration and invasion in gastric cancer[J]. Tissue Cell, 2021, 73: 101611.
16 CHENG Y, SUN H Z, WU L L, et al. VUp-regulation of VCAN promotes the proliferation, invasion and migration and serves as a biomarker in gastric cancer[J]. Onco Targets Ther, 2020, 13: 8665-8675.
17 PAPADAS A, ARAUZ G, CICALA A, et al. Versican and versican-matrikines in cancer progression, inflammation, and immunity[J]. J Histochem Cytochem, 2020, 68(12): 871-885.
18 WU Y J, LA PIERRE D P, WU J, et al. The interaction of versican with its binding partners[J]. Cell Res, 2005, 15(7): 483-494.
19 PAPADAS A, ASIMAKOPOULOS F. Versican in the tumor microenvironment[J]. Adv Exp Med Biol, 2020, 1272: 55-72.
20 KERN C B, NORRIS R A, THOMPSON R P, et al. Versican proteolysis mediates myocardial regression during outflow tract development[J]. Dev Dyn, 2007, 236(3): 671-683.
21 HAYES A, SUGAHARA K, FARRUGIA B, et al. Biodiversity of CS-proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis[J]. Biochem J, 2018, 475(3): 587-620.
22 KAMIYA N, WATANABE H, HABUCHI H, et al. Versican/PG-M regulates chondrogenesis as an extracellular matrix molecule crucial for mesenchymal condensation[J]. J Biol Chem, 2006, 281(4): 2390-2400.
23 FENG J, LI Y D, LI Y, et al. Versican promotes cardiomyocyte proliferation and cardiac repair[J]. Circulation, 2024, 149(13): 1004-1015.
24 WIGHT T N, KANG I, MERRILEES M J. Versican and the control of inflammation[J]. Matrix Biol, 2014, 35: 152-161.
25 MATSUMOTO K, SHIONYU M, GO M, et al. Distinct interaction of versican/PG-M with hyaluronan and link protein[J]. J Biol Chem, 2003, 278(42): 41205-41212.
26 DAY A J, MILNER C M. TSG-6: a multifunctional protein with anti-inflammatory and tissue-protective properties[J]. Matrix Biol, 2019, 78-79: 60-83.
27 WIGHT T N, KANG I, EVANKO S P, et al. Versican: a critical extracellular matrix regulator of immunity and inflammation[J]. Front Immunol, 2020, 11: 512.
28 TOCCHI A, PARKS W C. Functional interactions between matrix metalloproteinases and glycosaminoglycans[J]. FEBS J, 2013, 280(10): 2332-2341.
29 KANG I, HARTEN I A, CHANG M Y, et al. Versican deficiency significantly reduces lung inflammatory response induced by polyinosine-polycytidylic acid stimulation[J]. J Biol Chem, 2017, 292(1): 51-63.
30 DUTT S, KLéBER M, MATASCI M, et al. Versican V0 and V1 guide migratory neural crest cells[J]. J Biol Chem, 2006, 281(17): 12123-12131.
31 WU Y J, SHENG W, CHEN L W, et al. Versican V1 isoform induces neuronal differentiation and promotes neurite outgrowth[J]. Mol Biol Cell, 2004, 15(5): 2093-2104.
32 MERRILEES M J, BEAUMONT B W, BRAUN K R, et al. Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage accumulation[J]. Arterioscler Thromb Vasc Biol, 2011, 31(6): 1309-1316.
33 KANG I, YOON D W, BRAUN K R, et al. Expression of versican V3 by arterial smooth muscle cells alters tumor growth factor β (TGFβ)-, epidermal growth factor (EGF)-, and nuclear factor κB (NFκB)-dependent signaling pathways, creating a microenvironment that resists monocyte adhesion[J]. J Biol Chem, 2014, 289(22): 15393-15404.
34 KISCHEL P, WALTREGNY D, DUMONT B, et al. Versican overexpression in human breast cancer lesions: known and new isoforms for stromal tumor targeting[J]. Int J Cancer, 2010, 126(3): 640-650.
35 ZHANGYUAN G Y, WANG F, ZHANG H T, et al. VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR-PI3K-AKT pathway[J]. Oncogene, 2020, 39(6): 1213-1230.
36 TAN R Y, ZHANG G H, LIU R C, et al. Identification of early diagnostic and prognostic biomarkers via WGCNA in stomach adenocarcinoma[J]. Front Oncol, 2021, 11: 636461.
37 陆思芬, 魏小珍, 牟必琴, 等. 基于生物信息数据探究VCAN在食管鳞状细胞癌预后中的作用[J]. 中国胸心血管外科临床杂志, 2022, 29(8): 1031-1041.
37 LU S F, WEI X Z, MOU B Q, et al. Exploring the role of VCAN in the prognosis of esophageal squamous cell carcinoma based on bioinformatics data[J]. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(8): 1031-1041.
38 YAMAUCHI N, KANKE Y, SAITO K, et al. Stromal expression of cancer-associated fibroblast-related molecules, versican and lumican, is strongly associated with worse relapse-free and overall survival times in patients with esophageal squamous cell carcinoma[J]. Oncol Lett, 2021, 21(6): 445.
39 DESJARDINS M, XIE J, GURLER H, et al. Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids[J]. J Ovarian Res, 2014, 7: 70.
40 DU W W, YANG W N, YEE A J. Roles of versican in cancer biology: tumorigenesis, progression and metastasis[J]. Histol Histopathol, 2013, 28(6): 701-713.
41 YANG B L, ZHANG Y, CAO L, et al. Cell adhesion and proliferation mediated through the G1 domain of versican[J]. J Cell Biochem, 1999, 72(2): 210-220.
42 XUE J P, CHEN J N, SHEN Q, et al. Addition of high molecular weight hyaluronic acid to fibroblast-like stromal cells modulates endogenous hyaluronic acid metabolism and enhances proteolytic processing and secretion of versican[J]. Cells, 2020, 9(7): 1681.
43 CATTARUZZA S, SCHIAPPACASSI M, KIMATA K, et al. The globular domains of PG-M/versican modulate the proliferation-apoptosis equilibrium and invasive capabilities of tumor cells[J]. FASEB J, 2004, 18(6): 779-781.
44 SHENG W, WANG G Z, WANG Y, et al. The roles of versican V1 and V2 isoforms in cell proliferation and apoptosis[J]. Mol Biol Cell, 2005, 16(3): 1330-1340.
45 CHEN H, ZHAO Y, ZHANG J J, et al. Promoting effects of miR-135b on human multiple myeloma cells via regulation of the Wnt/β-catenin/versican signaling pathway[J]. Cytokine, 2021, 142: 155495.
46 ANG L C, ZHANG Y, CAO L, et al. Versican enhances locomotion of astrocytoma cells and reduces cell adhesion through its G1 domain[J]. J Neuropathol Exp Neurol, 1999, 58(6): 597-605.
47 YEUNG T L, LEUNG C S, WONG K K, et al. TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment[J]. Cancer Res, 2013, 73(16): 5016-5028.
48 杨迷玲, 杨金花, 王娜, 等. Versican与胃癌上皮-间质转化相关蛋白的表达及意义[J]. 医学研究杂志, 2022, 51(12): 69-74.
48 YANG M L, YANG J H, WANG N, et al. Expression of versican and its relationship with epithelial-mesenchymal transition related proteins and clinical significance in gastric cancer[J]. Journal of Medical Research, 2022, 51(12): 69-74.
49 DU W W, FANG L, YANG W N, et al. The role of versican G3 domain in regulating breast cancer cell motility including effects on osteoblast cell growth and differentiation in vitro: evaluation towards understanding breast cancer cell bone metastasis[J]. BMC Cancer, 2012, 12: 341.
50 DOS REIS D C, DAMASCENO K A, DE CAMPOS C B, et al. Versican and tumor-associated macrophages promotes tumor progression and metastasis in canine and murine models of breast carcinoma[J]. Front Oncol, 2019, 9: 577.
51 ZHENG P S, WEN J P, ANG L C, et al. Versican/PG-M G3 domain promotes tumor growth and angiogenesis[J]. FASEB J, 2004, 18(6): 754-756.
52 LABROPOULOU V T, THEOCHARIS A D, RAVAZOULA P, et al. Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours[J]. Histopathology, 2006, 49(6): 582-593.
53 EVANKO S P, POTTER-PERIGO S, BOLLYKY P L, et al. Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration[J]. Matrix Biol, 2012, 31(2): 90-100.
54 POTTER-PERIGO S, JOHNSON P Y, EVANKO S P, et al. Polyinosine-polycytidylic acid stimulates versican accumulation in the extracellular matrix promoting monocyte adhesion[J]. Am J Respir Cell Mol Biol, 2010, 43(1): 109-120.
55 KAUR A, ECKER B L, DOUGLASS S M, et al. Remodeling of the collagen matrix in aging skin promotes melanoma metastasis and affects immune cell motility[J]. Cancer Discov, 2019, 9(1): 64-81.
Outlines

/