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Osteopontin-4 and Osteopontin-5 splice variants are expressed in several tumor cell lines

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Abstract

Among osteopontin splice variants (OPN-SV), the expression profile of osteopontin-4 (OPN4) and osteopontin-5 (OPN5) has not been addressed in distinct cancer types. We herein aimed to investigate their expression in several cancer cell lines, besides comparing it in relation to the three previously described OPN-SV: OPNa, OPNb and OPNc. Total RNA from cancer cell lines, including prostate (PC3 and DU145), ovarian (A2780), breast (MCF-7 and MDA-MB-231), colorectal (Caco-2, HT-29 and HCT-116), thyroid (TT, TPC1 and 8505c) and lung (A549 and NCI-H460) was extracted, followed by cDNA synthesis. OPN-SV transcript analysis by RT-PCR or RT-qPCR were performed using OPN-SV specific oligonucleotides and gapdh and actin transcripts were used as housekeeping controls. OPN4 and OPN5 transcripts displayed co-expression in most tested cell lines. OPN4 was found expressed in similar or higher levels in relation to OPN5. Moreover, in most tested cell lines, OPN4 is also expressed in similar levels to OPNa or OPNb. The expression of OPN5 is also generally variable in relation to the other OPN-SV, but expressed in similar or higher levels in relation to OPNc, depending on each tested cell line. OPN4 and OPN5 seem to be co-expressed in several tumor types and OPN4 is one of the most overexpressed OPN-SV in distinct tumor cell lines. Once both OPN4 and OPN5 are differentially expressed and also evidence tumor-specific expression patterns, we hypothesize that similarly to the other OPN-SV, they also possibly contribute to key aspects of tumor progression, what should be further functionally investigated in distinct tumor models.

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Fig. 1
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Data availability

All raw data used to analyze these results are freely available on demand.

References

  1. Hao C, Cui Y, Owen S et al (2017) Human osteopontin: potential clinical applications in cancer (Review). Int J Mol Med 39:1327–1337. https://doi.org/10.3892/ijmm.2017.2964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shevde LA, Samant RS (2014) Role of osteopontin in the pathophysiology of cancer. Matrix Biol 37:131–141. https://doi.org/10.1016/j.matbio.2014.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bastos ACSF, Blunck CB, Emerenciano M, Gimba ERP (2017) Osteopontin and their roles in hematological malignancies: Splice variants on the new avenues. Cancer Lett 408:138–143. https://doi.org/10.1016/j.canlet.2017.08.022

    Article  CAS  PubMed  Google Scholar 

  4. Gimba ER, Tilli TM (2013) Human osteopontin splicing isoforms: known roles, potential clinical applications and activated signaling pathways. Cancer Lett 331:11–17. https://doi.org/10.1016/j.canlet.2012.12.003

    Article  CAS  PubMed  Google Scholar 

  5. Lamort A-S, Giopanou I, Psallidas I, Stathopoulos GT (2019) Osteopontin as a link between inflammation and cancer: the thorax in the Spotlight. Cells. https://doi.org/10.3390/cells8080815

    Article  PubMed  PubMed Central  Google Scholar 

  6. Leavenworth JW, Verbinnen B, Wang Q et al (2015) Intracellular osteopontin regulates homeostasis and function of natural killer cells. Proc Natl Acad Sci USA 112:494–499. https://doi.org/10.1073/pnas.1423011112

    Article  CAS  PubMed  Google Scholar 

  7. Urbanski LM, Leclair N, Anczuków O (2018) Alternative-splicing defects in cancer: splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics. Wiley Interdiscip Rev RNA 9:e1476. https://doi.org/10.1002/wrna.1476

    Article  PubMed  PubMed Central  Google Scholar 

  8. Martinez-Montiel N, Rosas-Murrieta NH, Anaya Ruiz M et al (2018) Alternative splicing as a target for cancer treatment. Int J Mol Sci. https://doi.org/10.3390/ijms19020545

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kozlovski I, Siegfried Z, Amar-Schwartz A, Karni R (2017) The role of RNA alternative splicing in regulating cancer metabolism. Hum Genet 136:1113–1127. https://doi.org/10.1007/s00439-017-1803-x

    Article  CAS  PubMed  Google Scholar 

  10. Saitoh Y, Kuratsu J, Takeshima H et al (1995) Expression of osteopontin in human glioma. Its correlation with the malignancy. Lab Invest 72:55–63

    CAS  PubMed  Google Scholar 

  11. Briones-Orta MA, Avendaño-Vázquez SE, Aparicio-Bautista DI et al (2017) Osteopontin splice variants and polymorphisms in cancer progression and prognosis. Biochim Biophys Acta Rev Cancer 1868:93–108. https://doi.org/10.1016/j.bbcan.2017.02.005

    Article  CAS  PubMed  Google Scholar 

  12. Cabiati M, Svezia B, Matteucci M et al (2016) Myocardial expression analysis of osteopontin and its splice variants in patients affected by end-stage idiopathic or ischemic dilated cardiomyopathy. PLoS One 11:e0160110. https://doi.org/10.1371/journal.pone.0160110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yan W, Qian C, Zhao P et al (2010) Expression pattern of osteopontin splice variants and its functions on cell apoptosis and invasion in glioma cells. Neuro Oncol 12:765–775. https://doi.org/10.1093/neuonc/noq006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tilli TM, Mello KD, Ferreira LB et al (2012) Both osteopontin-c and osteopontin-b splicing isoforms exert pro-tumorigenic roles in prostate cancer cells. Prostate 72:1688–1699. https://doi.org/10.1002/pros.22523

    Article  CAS  PubMed  Google Scholar 

  15. Tilli TM, Franco VF, Robbs BK et al (2011) Osteopontin-c splicing isoform contributes to ovarian cancer progression. Mol Cancer Res 9:280–293. https://doi.org/10.1158/1541-7786.MCR-10-0463

    Article  CAS  PubMed  Google Scholar 

  16. Zhao B, Sun T, Meng F et al (2011) Osteopontin as a potential biomarker of proliferation and invasiveness for lung cancer. J Cancer Res Clin Oncol 137:1061–1070. https://doi.org/10.1007/s00432-010-0968-7

    Article  CAS  PubMed  Google Scholar 

  17. Ferreira LB, Tavares C, Pestana A et al (2016) Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior. Oncotarget 7:52003–52016. https://doi.org/10.18632/oncotarget.10468

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ferreira LB, Eloy C, Pestana A et al (2016) Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma. Eur J Endocrinol 174:551–561. https://doi.org/10.1530/EJE-15-0577

    Article  CAS  PubMed  Google Scholar 

  19. Lin J, Myers AL, Wang Z et al (2015) Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma. Oncotarget 6:22239–22257. https://doi.org/10.18632/oncotarget.4161

    Article  PubMed  PubMed Central  Google Scholar 

  20. Viloria K, Hill NJ (2016) Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation. Biomol Concepts 7:117–132. https://doi.org/10.1515/bmc-2016-0004

    Article  CAS  PubMed  Google Scholar 

  21. Shinohara ML, Kim H-J, Kim J-H et al (2008) Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc Natl Acad Sci USA 105:7235–7239. https://doi.org/10.1073/pnas.0802301105

    Article  PubMed  Google Scholar 

  22. Zohar R, Suzuki N, Suzuki K et al (2000) Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration. J Cell Physiol 184:118–130. https://doi.org/10.1002/(SICI)1097-4652(200007)184:1<118:AID-JCP13>3.0.CO;2-Y

    Article  CAS  PubMed  Google Scholar 

  23. Sun S-J, Wu C-C, Sheu G-T et al (2016) Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth. Oncotarget 7:55572–55584. https://doi.org/10.18632/oncotarget.10865

    Article  PubMed  PubMed Central  Google Scholar 

  24. Goparaju CMV, Pass HI, Blasberg JD et al (2010) Functional heterogeneity of osteopontin isoforms in non-small cell lung cancer. J Thorac Oncol 5:1516–1523. https://doi.org/10.1097/JTO.0b013e3181eba6bd

    Article  PubMed  PubMed Central  Google Scholar 

  25. Orozco CA, Acevedo A, Cortina L et al (2013) The combined expression patterns of ikaros isoforms characterize different hematological tumor subtypes. PLoS One. https://doi.org/10.1371/journal.pone.0082411

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) [Grant Numbers E-26/010.002007/2014; E-26/203.204/2015]; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [Grant Numbers: 310591/2014-7; 312158/2017-3]; Ministério da Saúde (MS); Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação (PROPPI) da Universidade Federal Fluminense (UFF); Fundação do Câncer (Programa de Oncobiologia).

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Authors and Affiliations

  1. Programa de Oncobiologia Celular e Molecular, Instituto Nacional de Câncer, Rua André Cavalcanti, 37, 3° andar, Rio de Janeiro, CEP: 20 231 050, Brazil

    Gabriela Ribeiro Silva, Daniella Santos Mattos, Ana Clara Fonseca Bastos, Bruna Prunes Pena Baroni Viana, Mariana Concentino Menezes Brum, Luciana Bueno Ferreira & Etel Rodrigues Pereira Gimba

  2. Programa de Pós-Graduação Stricto Sensu em Oncologia, Instituto Nacional de Câncer, Rua André Cavalcanti, 37, 3° andar, Rio de Janeiro, CEP: 20 231 050, Brazil

    Daniella Santos Mattos, Ana Clara Fonseca Bastos, Bruna Prunes Pena Baroni Viana, Mariana Concentino Menezes Brum, Luciana Bueno Ferreira & Etel Rodrigues Pereira Gimba

  3. Divisão de Pesquisa Clínica, Instituto Nacional de Câncer, Rua André Cavalcanti, 37, 3° andar, Rio de Janeiro, CEP: 20 231 050, Brazil

    Etel Rodrigues Pereira Gimba

  4. Departamento de Ciências da Natureza, Instituto de Humanidades E Saúde, Universidade Federal Fluminense, Rua Recife 1-7, Bairro Bela Vista, Rio das Ostras, RJ, CEP 28880-000, Brazil

    Etel Rodrigues Pereira Gimba

  5. Programa de Pós-Graduação Em Ciências Biomédicas, Fisiologia E Farmacologia, Instituto Biomédico, Av. Prof. Hernani Melo, Niterói, 101, CEP24210-130, Brazil

    Gabriela Ribeiro Silva & Etel Rodrigues Pereira Gimba

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  1. Gabriela Ribeiro Silva
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  2. Daniella Santos Mattos
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  3. Ana Clara Fonseca Bastos
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  4. Bruna Prunes Pena Baroni Viana
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  5. Mariana Concentino Menezes Brum
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  6. Luciana Bueno Ferreira
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  7. Etel Rodrigues Pereira Gimba
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Contributions

GR performed most experiments, in conjunction with DM; ACFB, BP, MCMB; GR and DM analyzed the data and cultured cell lines; LBF supervised the students, analyzed the data and revised the manuscript; ERPG supervised the students, conceptualized the study, drafted and revised the manuscript, coordinated the study and provided financial support.

Corresponding author

Correspondence to Etel Rodrigues Pereira Gimba.

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Silva, G.R., Mattos, D.S., Bastos, A.C.F. et al. Osteopontin-4 and Osteopontin-5 splice variants are expressed in several tumor cell lines. Mol Biol Rep 47, 8339–8345 (2020). https://doi.org/10.1007/s11033-020-05867-9

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  • DOI: https://doi.org/10.1007/s11033-020-05867-9

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