OpenLB
Open Library of Bioscience
Advanced Search
Methods in molecular biology (Clifton, N.J.)
2022;2442 685-711.

Exploring the Role of Galectins in Cancer : In Vitro and In Vivo Approaches.

Neus Martínez-Bosch, Noemí Manero-Rupérez, Mireia Moreno, Pilar Navarro
Author Information
  1. Neus Martínez-Bosch: Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, Barcelona, Spain.
  2. Noemí Manero-Rupérez: Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, Barcelona, Spain.
  3. Mireia Moreno: Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, Barcelona, Spain.
  4. Pilar Navarro: Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, Barcelona, Spain. pnavarro@imim.es.
PMID: 35320553 DOI: 10.1007/978-1-0716-2055-7_37

Abstract

Galectins have been linked to tumorigenesis since 1975, even before this family of proteins was given its name. Since then, hundreds of papers have analyzed the role of different galectins in cancer development and progression, deciphering their involvement in many different pathological events, from the regulation of cell cycle, to angiogenesis, metastasis, and immune attack evasion. Importantly, the tumor galectin profile is often altered in many cancers and aberrant levels of some of the members of this family have been considered in diagnosis and frequently correlated with patient prognosis and clinicopathological characteristics. In this chapter, we summarize most frequent techniques employed in cancer research to interrogate the role of galectins, using Gal-1 to illustrate one member of the family and pancreatic cancer as an experimental model. We will cover from techniques employed to detect their expression (tissue and blood samples) to the most frequent tools used to change expression levels and the cell line-based in vitro studies and murine preclinical models used to explore their role in tumor progression and/or clinical translation.

Keywords

Anchorage independent growth Biomarker Cancer Downregulation ELISA Galectin-1 Genetically engineered mouse Immunohistochemistry Invasion Knockdown Migration Overexpression PCR Proliferation Viability

References

  1. Stowell SR, Ju T, Cummings RD (2015) Protein glycosylation in cancer. Annu Rev Pathol 10:473–510. https://doi.org/10.1146/annurev-pathol-012414-040438 [DOI: 10.1146/annurev-pathol-012414-040438]
  2. Pinho SS, Reis CA (2015) Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 15:540–555. https://doi.org/10.1038/nrc3982 [DOI: 10.1038/nrc3982]
  3. Rabinovich GA, Croci DO (2012) Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 36:322–335 [DOI: 10.1016/j.immuni.2012.03.004]
  4. Yang RY, Rabinovich GA, Liu FT (2008) Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 10:e17. https://doi.org/10.1017/S1462399408000719 [DOI: 10.1017/S1462399408000719]
  5. Thijssen VL, Heusschen R, Caers J, Griffioen AW (2015) Galectin expression in cancer diagnosis and prognosis: a systematic review. Biochim Biophys Acta 1855:235–247. https://doi.org/10.1016/j.bbcan.2015.03.003 [DOI: 10.1016/j.bbcan.2015.03.003]
  6. Hanahan D, Weinberg RAA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013 [DOI: 10.1016/j.cell.2011.02.013]
  7. Girotti MR, Salatino M, Dalotto-Moreno T, Rabinovich GA (2020) Sweetening the hallmarks of cancer: galectins as multifunctional mediators of tumor progression. J Exp Med 217:e20182041. https://doi.org/10.1084/jem.20182041 [DOI: 10.1084/jem.20182041]
  8. Astorgues-Xerri L, Riveiro ME, Tijeras-Raballand A, Serova M, Neuzillet C, Albert S et al (2014) Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treat Rev 40:307–319. https://doi.org/10.1016/j.ctrv.2013.07.007 [DOI: 10.1016/j.ctrv.2013.07.007]
  9. Rabinovich GA (2005) Galectin-1 as a potential cancer target. Br J Cancer 92:1188–1192 [DOI: 10.1038/sj.bjc.6602493]
  10. Martinez-Bosch N, Barranco LE, Orozco CA, Moreno M, Visa L, Iglesias M et al (2018) Increased plasma levels of galectin-1 in pancreatic cancer: potential use as biomarker. Oncotarget 9:32984–32996. https://doi.org/10.18632/oncotarget.26034 [DOI: 10.18632/oncotarget.26034]
  11. Méndez-Huergo SP, Blidner AG, Rabinovich GA (2017) Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis. Curr Opin Immunol 45:8–15. https://doi.org/10.1016/j.coi.2016.12.003 [DOI: 10.1016/j.coi.2016.12.003]
  12. Cerliani JP, Blidner AG, Toscano MA, Croci DO, Rabinovich GA (2017) Translating the “Sugar Code” into immune and vascular signaling programs. Trends Biochem Sci 42:255–273. https://doi.org/10.1016/j.tibs.2016.11.003 [DOI: 10.1016/j.tibs.2016.11.003]
  13. Martínez-Bosch N, Navarro P (2020) Galectins in the tumor microenvironment: focus on galectin-1. In: Birbrair A (ed) Tumor microenvironment, Advances in experimental medicine and biology, vol 1259. Springer, Cham [DOI: 10.1007/978-3-030-43093-1_2]
  14. Martínez-Bosch N, Fern̊andez-Barrena MG, Moreno M, Ortiz-Zapater E, Munn̊e-Collado J, Iglesias M et al (2014) Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and hedgehog signaling activation. Cancer Res 74:3512–3524. https://doi.org/10.1158/0008-5472.CAN-13-3013 [DOI: 10.1158/0008-5472.CAN-13-3013]
  15. Orozco CACA, Martinez-Bosch N, Guerrero PEPE, Vinaixa J, Dalotto-Moreno T, Iglesias M et al (2018) Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor–stroma crosstalk. Proc Natl Acad Sci U S A 115:E3769–E3778. https://doi.org/10.1073/pnas.1722434115 [DOI: 10.1073/pnas.1722434115]
  16. Liu FT, Rabinovich GA (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5:29–41 [DOI: 10.1038/nrc1527]
  17. Paz A, Haklai R, Elad-Sfadia G, Ballan E, Kloog Y (2001) Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene 20:7486–7493 [DOI: 10.1038/sj.onc.1204950]
  18. Chung L-Y, Tang S-J, Sun G-H, Chou T-Y, Yeh T-S, Yu S-L et al (2012) Galectin-1 promotes lung cancer progression and chemoresistance by upregulating p38 MAPK, ERK, and cyclooxygenase-2. Clin Cancer Res 18:4037–4047. https://doi.org/10.1158/1078-0432.CCR-11-3348 [DOI: 10.1158/1078-0432.CCR-11-3348]
  19. van den Brûle F, Califice S, Garnier F, Fernandez PL, Berchuck A, Castronovo V (2003) Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Lab Investig 83:377–386 [DOI: 10.1097/01.LAB.0000059949.01480.40]
  20. Toscano MA, Bianco GA, Ilarregui JM, Croci DO, Correale J, Hernandez JD et al (2007) Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8:825–834 [DOI: 10.1038/ni1482]
  21. Liu SD, Tomassian T, Bruhn KW, Miller JF, Poirier F, Miceli MC (2009) Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size. J Immunol 182:5283–5295. https://doi.org/10.4049/jimmunol.0803811 [DOI: 10.4049/jimmunol.0803811]
  22. Croci DO, Cerliani JP, Dalotto-Moreno T, Méndez-Huergo SP, Mascanfroni ID, Dergan-Dylon S et al (2014) Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell 156:744–758. https://doi.org/10.1016/j.cell.2014.01.043 [DOI: 10.1016/j.cell.2014.01.043]
  23. Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD, Brinster RL (1991) Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci U S A 88:93–97 [DOI: 10.1073/pnas.88.1.93]
  24. Guerra C, Schuhmacher AJ, Cañamero M, Grippo PJ, Verdaguer L, Pérez-Gallego L et al (2007) Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11:291–302. https://doi.org/10.1016/j.ccr.2007.01.012 [DOI: 10.1016/j.ccr.2007.01.012]
  25. Poirier F, Robertson EJ (1993) Normal development of mice carrying a null mutation in the gene encoding the L14 S-type lectin. Development 119:1229–1236 [DOI: 10.1242/dev.119.4.1229]
  26. Camby I, Le Mercier M, Lefranc F, Kiss R (2006) Galectin-1: a small protein with major functions. Glycobiology 16:137R–157R [DOI: 10.1093/glycob/cwl025]
  27. Nangia-Makker P, Balan V, Raz A (2012) Galectin-3 binding and metastasis. Methods Mol Biol 878:251–266. https://doi.org/10.1007/978-1-61779-854-2_17 [DOI: 10.1007/978-1-61779-854-2_17]
  28. Ueda S, Kuwabara I, Liu F-T (2004) Suppression of tumor growth by galectin-7 gene transfer. Cancer Res 64:5672–5676. https://doi.org/10.1158/0008-5472.CAN-04-0985 [DOI: 10.1158/0008-5472.CAN-04-0985]
  29. Ireson CR, Alavijeh MS, Palmer AM, Fowler ER, Jones HJ (2019) The role of mouse tumour models in the discovery and development of anticancer drugs. Br J Cancer 121:101–108. https://doi.org/10.1038/s41416-019-0495-5 [DOI: 10.1038/s41416-019-0495-5]
  30. Rabinovich GA, Conejo-García JR (2016) Shaping the immune landscape in cancer by galectin-driven regulatory pathways. J Mol Biol 428:3266–3281. https://doi.org/10.1016/j.jmb.2016.03.021 [DOI: 10.1016/j.jmb.2016.03.021]
  31. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823. https://doi.org/10.1126/science.1231143 [DOI: 10.1126/science.1231143]
  32. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE et al (2013) RNA-guided human genome engineering via Cas9. Science 339:823–826. https://doi.org/10.1126/science.1232033 [DOI: 10.1126/science.1232033]
  33. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F (2013) Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8:2281–2308. https://doi.org/10.1038/nprot.2013.143 [DOI: 10.1038/nprot.2013.143]
  34. Sanjana NE, Shalem O, Zhang F (2014) Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods 11:783–784. https://doi.org/10.1038/nmeth.3047 [DOI: 10.1038/nmeth.3047]
  35. Maybruck BT, Pfannenstiel LW, Diaz-Montero M, Gastman BR (2017) Tumor-derived exosomes induce CD8+ T cell suppressors. J Immunother Cancer 5(1):65. https://doi.org/10.1186/s40425-017-0269-7 [DOI: 10.1186/s40425-017-0269-7]
  36. Feng C, Nita-Lazar M, González-Montalbán N, Wang J, Mancini J, Ravindran C et al (2015) Manipulating galectin expression in zebrafish (Danio rerio). Methods Mol Biol 1207:327–341. https://doi.org/10.1007/978-1-4939-1396-1_22 [DOI: 10.1007/978-1-4939-1396-1_22]

MeSH Term

Animals
Carcinogenesis
Cell Transformation, Neoplastic
Galectins
Humans
Mice
Neoplasms, Experimental
Pancreatic Neoplasms

Chemicals

Galectins
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0familyrolecancerGalectinsdifferentgalectinsprogressionmanycelltumorlevelsfrequenttechniquesemployedexpressionusedCancerlinkedtumorigenesissince1975evenproteinsgivennameSincehundredspapersanalyzeddevelopmentdecipheringinvolvementpathologicaleventsregulationcycleangiogenesismetastasisimmuneattackevasionImportantlygalectinprofileoftenalteredcancersaberrantmembersconsidereddiagnosisfrequentlycorrelatedpatientprognosisclinicopathologicalcharacteristicschaptersummarizeresearchinterrogateusingGal-1illustrateonememberpancreaticexperimentalmodelwillcoverdetecttissuebloodsamplestoolschangeline-basedvitrostudiesmurinepreclinicalmodelsexploreand/orclinicaltranslationExploringRole:VitroVivoApproachesAnchorageindependentgrowthBiomarkerDownregulationELISAGalectin-1GeneticallyengineeredmouseImmunohistochemistryInvasionKnockdownMigrationOverexpressionPCRProliferationViability

Similar Articles

Cited By