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Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer

  • Authors:
    • Jinxiu Zhang
    • Kecheng Liu
    • Peng Peng
    • Siman Li
    • Zhe Ye
    • Yingjie Su
    • Shiquan Liu
    • Mengbin Qin
    • Jiean Huang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1163-1170
    |
    Published online on: May 30, 2019
       https://doi.org/10.3892/ol.2019.10417
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Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Unlike endothelium‑dependent vasculature, vasculogenic mimicry (VM) is an alternative type of blood supply in tumors that is frequently associated with poor patient outcome. Nectin‑4 serves a vital role in the formation and maintenance of adherens junctions; integrin β‑1 (ITGB1) promotes tumor invasion, metastasis and VM formation. In the present study, the analysis of nectin‑4 mRNA expression in a database of The Cancer Genome Atlas (TCGA) was combined with that of another non‑overlapping cohort of 68 patients with CRC. TCGA data were used to examine nectin‑4 mRNA expression in CRC and its correlation with the clinicopathological features of patients. Data from the non‑overlapping cohort of patients was used to determine nectin‑4 and ITGB1 protein expression in CRC by immunohistochemical (IHC) staining. Cluster of differentiation 34/periodic acid‑Schiff double staining was performed to validate the presence of VM formation. The association with, and significance of combining nectin‑4, ITGB1 protein expression and VM formation for predicting patient prognosis was evaluated. The TCGA dataset demonstrated that nectin‑4 mRNA was upregulated in CRC, which was significantly relate to lymph node metastasis (P=0.0017), distant metastasis (P=0.0045), and tumor‑node‑metastasis (TNM) stage (P=0.0015). Of the 68 patients analyzed by IHC staining, 48 (70.6%) were positive for nectin‑4, 46 (67.6%) for ITGB1 and 17 (25%) for VM formation. Nectin‑4 protein expression was associated with ITGB1 protein expression (P<0.01) and VM formation (P<0.05). Nectin‑4, ITGB1 expression and VM formation were associated with distant metastasis stage (P<0.05) and TNM stage (P<0.05). Based on these findings it was concluded that nectin‑4 was upregulated in CRC tissues compared with normal mucosal tissues, and was associated with ITGB1 expression and VM formation. Furthermore, nectin‑4 and ITGB1 protein expression, together with VM formation may be used to predict poor prognosis in CRC.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R and Jemal A: Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 66:271–289. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Takai Y, Miyoshi J, Ikeda W and Ogita H: Nectins and nectin-like molecules: Roles in contact inhibition of cell movement and proliferation. Nature reviews. Nat Rev Mol Cell Biol. 9:603–615. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Rajc J, Gugić D, Fröhlich I, Marjanović K and Dumenčić B: Prognostic role of Nectin-4 expression in luminal B (HER2 negative) breast cancer. Pathol Res Pract. 213:1102–1108. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Reymond N, Fabre S, Lecocq E, Adelaide J, Dubreuil P and Lopez M: Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. J Biol Chem. 276:43205–43215. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Brancati F, Fortugno P, Bottillo I, Lopez M, Josselin E, Boudghene-Stambouli O, Agolini E, Bernardini L, Bellacchio E, Iannicelli M, et al: Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. Am J Hum Genet. 87:265–273. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Derycke MS, Pambuccian SE, Gilks CB, Kalloger SE, Ghidouche A, Lopez M, Bliss RL, Geller MA, Argenta PA, Harrington KM and Skubitz AP: Nectin 4 overexpression in ovarian cancer tissues and serum: Potential role as a serum biomarker. Am J Clin Pathol. 134:835–845. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Fabre-Lafay S, Monville F, Garrido-Urbani S, Berruyer-Pouyet C, Ginestier C, Reymond N, Finetti P, Sauvan R, Adélaïde J, Geneix J, et al: Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer. 7:732007. View Article : Google Scholar : PubMed/NCBI

9 

Takano A, Ishikawa N, Nishino R, Masuda K, Yasui W, Inai K, Nishimura H, Ito H, Nakayama H, Miyagi Y, et al: Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res. 69:6694–6703. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Bianconi D, Unseld M and Prager GW: Integrins in the spotlight of cancer. Int J Mol Sci. 17(pii): E20372016. View Article : Google Scholar : PubMed/NCBI

11 

Duro-Castano A, Gallon E, Decker C and Vicent MJ: Modulating angiogenesis with integrin-targeted nanomedicines. Adv Drug Deliv Rev. 119:101–119. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Vartanian A, Stepanova E, Grigorieva I, Solomko E, Belkin V, Baryshnikov A and Lichinitser M: Melanoma vasculogenic mimicry capillary-like structure formation depends on integrin and calcium signaling. Microcirculation. 18:390–399. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Camorani S, Crescenzi E, Gramanzini M, Fedele M, Zannetti A and Cerchia L: Aptamer-mediated impairment of EGFR-integrin αvβ3 complex inhibits vasculogenic mimicry and growth of triple-negative breast cancers. Sci Rep. 7:466592017. View Article : Google Scholar : PubMed/NCBI

14 

Velez DO, Tsui B, Goshia T, Chute CL, Han A, Carter H and Fraley SI: 3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry. Nat Commun. 8:16512017. View Article : Google Scholar : PubMed/NCBI

15 

Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS and Hendrix MJ: Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry. Am J Pathol. 155:739–752. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Qiao L, Liang N, Zhang J, Xie J, Liu F, Xu D, Yu X and Tian Y: Advanced research on vasculogenic mimicry in cancer. J Cell Mol Med. 19:315–326. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Wei L, Jin Z, Yang S, Xu Y, Zhu Y and Ji Y: TCGA-assembler 2: Software pipeline for retrieval and processing of TCGA/CPTAC data. Bioinformatics. 34:1615–1617. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Benson AB III, Venook AP, Cederquist L, Chan E, Chen YJ, Cooper HS, Deming D, Engstrom PF, Enzinger PC, Fichera A, et al: Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 15:370–398. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Sadeghi MR, Jeddi F, Soozangar N, Somi MH, Shirmohamadi M, Khaze V and Samadi N: Nrf2/P-glycoprotein axis is associated with clinicopathological characteristics in colorectal cancer. Biomed Pharmacother. 104:458–464. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Kurita S, Ogita H and Takai Y: Cooperative role of nectin-nectin and nectin-afadin interactions in formation of nectin-based cell-cell adhesion. J Biol Chem. 286:36297–36303. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Pavlova NN, Pallasch C, Elia AE, Braun CJ, Westbrook TF, Hemann M and Elledge SJ: A role for PVRL4-driven cell-cell interactions in tumorigenesis. ELife. 2:e003582013. View Article : Google Scholar : PubMed/NCBI

22 

Siddharth S, Goutam K, Das S, Nayak A, Nayak D, Sethy C, Wyatt MD and Kundu CN: Nectin-4 is a breast cancer stem cell marker that induces WNT/β-catenin signaling via Pi3k/Akt axis. Int J Biochem Cell Biol. 89:85–94. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Cao Z, Bao M, Miele L, Sarkar FH, Wang Z and Zhou Q: Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: A systemic review and meta-analysis. Eur J Cancer. 49:3914–3923. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Zhang J, Qiao L, Liang N, Xie J, Luo H, Deng G and Zhang J: Vasculogenic mimicry and tumor metastasis. J BUON. 21:533–541. 2016.PubMed/NCBI

25 

Sun B, Zhang D, Zhao N and Zhao X: Epithelial-to-endothelial transition and cancer stem cells: Two cornerstones of vasculogenic mimicry in malignant tumors. Oncotarget. 8:30502–30510. 2017.PubMed/NCBI

26 

Dey N, De P and Brian LJ: Evading anti-angiogenic therapy: Resistance to anti-angiogenic therapy in solid tumors. Am J Transl Res. 7:1675–1698. 2015.PubMed/NCBI

27 

Chen MB, Lamar JM, Li R, Hynes RO and Kamm RD: Elucidation of the roles of tumor integrin beta1 in the extravasation stage of the metastasis cascade. Cancer Res. 76:2513–2524. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Xu Z, Zou L, Ma G, Wu X, Huang F, Feng T, Li S, Lin Q, He X, Liu Z and Cao X: Integrin β1 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma. Am J Cancer Res. 7:531–542. 2017.PubMed/NCBI

29 

Zhang Y, Liu S, Wang L, Wu Y, Hao J, Wang Z, Lu W, Wang XA, Zhang F, Cao Y, et al: A novel PI3K/AKT signaling axis mediates Nectin-4-induced gallbladder cancer cell proliferation, metastasis and tumor growth. Cancer Lett. 375:179–189. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Liu K, Peng P, Li S, Ye Z, Su Y, Liu S, Qin M and Huang J: Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer. Oncol Lett 18: 1163-1170, 2019.
APA
Zhang, J., Liu, K., Peng, P., Li, S., Ye, Z., Su, Y. ... Huang, J. (2019). Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer. Oncology Letters, 18, 1163-1170. https://doi.org/10.3892/ol.2019.10417
MLA
Zhang, J., Liu, K., Peng, P., Li, S., Ye, Z., Su, Y., Liu, S., Qin, M., Huang, J."Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer". Oncology Letters 18.2 (2019): 1163-1170.
Chicago
Zhang, J., Liu, K., Peng, P., Li, S., Ye, Z., Su, Y., Liu, S., Qin, M., Huang, J."Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer". Oncology Letters 18, no. 2 (2019): 1163-1170. https://doi.org/10.3892/ol.2019.10417
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Liu K, Peng P, Li S, Ye Z, Su Y, Liu S, Qin M and Huang J: Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer. Oncol Lett 18: 1163-1170, 2019.
APA
Zhang, J., Liu, K., Peng, P., Li, S., Ye, Z., Su, Y. ... Huang, J. (2019). Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer. Oncology Letters, 18, 1163-1170. https://doi.org/10.3892/ol.2019.10417
MLA
Zhang, J., Liu, K., Peng, P., Li, S., Ye, Z., Su, Y., Liu, S., Qin, M., Huang, J."Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer". Oncology Letters 18.2 (2019): 1163-1170.
Chicago
Zhang, J., Liu, K., Peng, P., Li, S., Ye, Z., Su, Y., Liu, S., Qin, M., Huang, J."Upregulation of nectin‑4 is associated with ITGB1 and vasculogenic mimicry and may serve as a predictor of poor prognosis in colorectal cancer". Oncology Letters 18, no. 2 (2019): 1163-1170. https://doi.org/10.3892/ol.2019.10417
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