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Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Prognostic relevance of LGALS3BP in human colorectal carcinoma

Authors: Enza Piccolo, Nicola Tinari, Domenica D’Addario, Cosmo Rossi, Valentina Iacobelli, Rossana La Sorda, Rossano Lattanzio, Maurizia D’Egidio, Annalisa Di Risio, Mauro Piantelli, Pier Giorgio Natali, Stefano Iacobelli

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

Background

A previous report has shown that LGALS3BP (also known as 90K or Mac-2 BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin. The role of LGALS3BP in CRC prognosis was investigated.

Methods

The role of LGALS3BP on CRC progression and clinical prognosis was analyzed by combining cell cultures, in vitro assays, and immunohistochemistry.

Results

Silencing of LGALS3BP in HCT-116 human colon cancer cells resulted in enhanced β-catenin expression that was reversed by addition of human recombinant LGALS3BP. Moreover, intra-tumor delivery of LGALS3BP reduced tumor growth of xenografts originating from LGALS3BP-silenced HCT-116 cells. Finally, in a series of 196 CRC patients, LGALS3BP expression in tumor tissue associated with clinical outcome. Patients with high LGALS3BP expression had lower risk of relapse and a longer overall survival time than those with low LGALS3BP expression. Multivariate analyses confirmed LGALS3BP expression status as the only independent prognostic factor of survival.

Conclusions

These results provide evidence that low expression of LGALS3BP participates in malignant progression of CRC and implicates poor prognosis, highlighting its augmentation as a potential therapeutic approach.
Literature
1.
go back to reference Andre T, Quinaux E, Louvet C, Colin P, Gamelin E, Bouche O et al (2007) Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol 25:3732–3738PubMedCrossRef Andre T, Quinaux E, Louvet C, Colin P, Gamelin E, Bouche O et al (2007) Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol 25:3732–3738PubMedCrossRef
2.
go back to reference Gill S, Loprinzi CL, Sargent DJ, Thome SD, Alberts SR, Haller DG et al (2004) Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 22:1797–1806PubMedCrossRef Gill S, Loprinzi CL, Sargent DJ, Thome SD, Alberts SR, Haller DG et al (2004) Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 22:1797–1806PubMedCrossRef
3.
go back to reference Mamounas E, Wieand S, Wolmark N, Bear HD, Atkins JN, Song K et al (1999) Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ B versus Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol 17:1349–1355PubMed Mamounas E, Wieand S, Wolmark N, Bear HD, Atkins JN, Song K et al (1999) Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ B versus Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol 17:1349–1355PubMed
4.
go back to reference Iacobelli S, Arno E, D’Orazio A, Coletti G (1986) Detection of antigens recognized by a novel monoclonal antibody in tissue and serum from patients with breast cancer. Cancer Res 46:3005–3010PubMed Iacobelli S, Arno E, D’Orazio A, Coletti G (1986) Detection of antigens recognized by a novel monoclonal antibody in tissue and serum from patients with breast cancer. Cancer Res 46:3005–3010PubMed
5.
go back to reference Koths K, Taylor E, Halenbeck R, Casipit C, Wang A (1993) Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain. J Biol Chem 268:14245–14249PubMed Koths K, Taylor E, Halenbeck R, Casipit C, Wang A (1993) Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain. J Biol Chem 268:14245–14249PubMed
6.
go back to reference Grassadonia A, Tinari N, Iurisci I, Piccolo E, Cumashi A, Innominato P et al (2004) 90K (Mac-2 BP) and galectins in tumor progression and metastasis. Glycoconj J 19:551–556PubMedCrossRef Grassadonia A, Tinari N, Iurisci I, Piccolo E, Cumashi A, Innominato P et al (2004) 90K (Mac-2 BP) and galectins in tumor progression and metastasis. Glycoconj J 19:551–556PubMedCrossRef
7.
go back to reference Iacobelli S, Sismondi P, Giai M, D’Egidio M, Tinari N, Amatetti C et al (1994) Prognostic value of a novel circulating serum 90K antigen in breast cancer. Br J Cancer 69:172–176PubMedCentralPubMedCrossRef Iacobelli S, Sismondi P, Giai M, D’Egidio M, Tinari N, Amatetti C et al (1994) Prognostic value of a novel circulating serum 90K antigen in breast cancer. Br J Cancer 69:172–176PubMedCentralPubMedCrossRef
8.
go back to reference Tinari N, Lattanzio R, Querzoli P, Natoli C, Grassadonia A, Alberti S et al (2009) High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies. Int J Cancer 124:333–338PubMedCrossRef Tinari N, Lattanzio R, Querzoli P, Natoli C, Grassadonia A, Alberti S et al (2009) High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies. Int J Cancer 124:333–338PubMedCrossRef
9.
go back to reference Correale M, Giannuzzi V, Iacovazzi PA, Valenza MA, Lanzillotta S, Abbate I et al (1999) Serum 90K/MAC-2BP glycoprotein levels in hepatocellular carcinoma and cirrhosis. Anticancer Res 19:3469–3472PubMed Correale M, Giannuzzi V, Iacovazzi PA, Valenza MA, Lanzillotta S, Abbate I et al (1999) Serum 90K/MAC-2BP glycoprotein levels in hepatocellular carcinoma and cirrhosis. Anticancer Res 19:3469–3472PubMed
10.
go back to reference Iacovazzi PA, Notarnicola M, Caruso MG, Guerra V, Frisullo S, Altomare DF (2010) Serum levels of galectin-3 and its ligand 90k/mac-2 bp in colorectal cancer patients. Immunopharmacol Immunotoxicol 32:160–164PubMedCrossRef Iacovazzi PA, Notarnicola M, Caruso MG, Guerra V, Frisullo S, Altomare DF (2010) Serum levels of galectin-3 and its ligand 90k/mac-2 bp in colorectal cancer patients. Immunopharmacol Immunotoxicol 32:160–164PubMedCrossRef
11.
go back to reference Strizzi L, Muraro R, Vianale G, Natoli C, Talone L, Catalano A et al (2002) Expression of glycoprotein 90K in human malignant pleural mesothelioma: correlation with patient survival. J Pathol 197:218–223PubMedCrossRef Strizzi L, Muraro R, Vianale G, Natoli C, Talone L, Catalano A et al (2002) Expression of glycoprotein 90K in human malignant pleural mesothelioma: correlation with patient survival. J Pathol 197:218–223PubMedCrossRef
12.
go back to reference Kunzli BM, Berberat PO, Zhu ZW, Martignoni M, Kleeff J, Tempia-Caliera AA et al (2002) Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma. Cancer 94:228–239PubMedCrossRef Kunzli BM, Berberat PO, Zhu ZW, Martignoni M, Kleeff J, Tempia-Caliera AA et al (2002) Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma. Cancer 94:228–239PubMedCrossRef
13.
go back to reference Marchetti A, Tinari N, Buttitta F, Chella A, Angeletti CA, Sacco R et al (2002) Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients. Cancer Res 62:2535–2539PubMed Marchetti A, Tinari N, Buttitta F, Chella A, Angeletti CA, Sacco R et al (2002) Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients. Cancer Res 62:2535–2539PubMed
14.
go back to reference Morandi F, Corrias MV, Levreri I, Scaruffi P, Raffaghello L, Carlini B et al (2011) Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients. Cancer Immunol Immunother 60:1485–1495PubMedCentralPubMedCrossRef Morandi F, Corrias MV, Levreri I, Scaruffi P, Raffaghello L, Carlini B et al (2011) Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients. Cancer Immunol Immunother 60:1485–1495PubMedCentralPubMedCrossRef
15.
go back to reference Zambelli D, Zuntini M, Nardi F, Manara MC, Serra M, Landuzzi L et al (2010) Biological indicators of prognosis in Ewing’s sarcoma: an emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP). Int J Cancer 126:41–52PubMedCrossRef Zambelli D, Zuntini M, Nardi F, Manara MC, Serra M, Landuzzi L et al (2010) Biological indicators of prognosis in Ewing’s sarcoma: an emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP). Int J Cancer 126:41–52PubMedCrossRef
16.
go back to reference Lee JH, Bae JA, Lee JH, Seo YW, Kho DH, Sun EG et al (2010) Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/beta-catenin signal via ISGylation of beta-catenin. Gut 59:907–917PubMedCrossRef Lee JH, Bae JA, Lee JH, Seo YW, Kho DH, Sun EG et al (2010) Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/beta-catenin signal via ISGylation of beta-catenin. Gut 59:907–917PubMedCrossRef
17.
go back to reference Piccolo E, Tinari N, Semeraro D, Traini S, Fichera I, Cumashi A et al (2013) LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis. J Mol Med (Berl) 91:83–94CrossRef Piccolo E, Tinari N, Semeraro D, Traini S, Fichera I, Cumashi A et al (2013) LGALS3BP, lectin galactoside-binding soluble 3 binding protein, induces vascular endothelial growth factor in human breast cancer cells and promotes angiogenesis. J Mol Med (Berl) 91:83–94CrossRef
18.
go back to reference Silvestri B, Calderazzo F, Coppola V, Rosato A, Iacobelli S, Natoli C et al (1998) Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family. Clin Exp Immunol 113:394–400PubMedCentralPubMedCrossRef Silvestri B, Calderazzo F, Coppola V, Rosato A, Iacobelli S, Natoli C et al (1998) Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family. Clin Exp Immunol 113:394–400PubMedCentralPubMedCrossRef
19.
go back to reference Sasaki T, Brakebusch C, Engel J, Timpl R (1998) Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta1 integrins, collagens and fibronectin. EMBO J 17:1606–1613PubMedCentralPubMedCrossRef Sasaki T, Brakebusch C, Engel J, Timpl R (1998) Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta1 integrins, collagens and fibronectin. EMBO J 17:1606–1613PubMedCentralPubMedCrossRef
20.
go back to reference Lattanzio R, Marchisio M, La Sorda R, Tinari N, Falasca M, Alberti S et al (2013) Overexpression of activated phospholipase Cgamma1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy. Int J Cancer 132:1022–1031PubMedCrossRef Lattanzio R, Marchisio M, La Sorda R, Tinari N, Falasca M, Alberti S et al (2013) Overexpression of activated phospholipase Cgamma1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy. Int J Cancer 132:1022–1031PubMedCrossRef
21.
go back to reference Iacovazzi PA, Guerra V, Elba S, Sportelli F, Manghisi OG, Correale M (2003) Are 90K/MAC-2BP serum levels correlated with poor prognosis in HCC patients? Preliminary results. Int J Biol Markers 18:222–226PubMed Iacovazzi PA, Guerra V, Elba S, Sportelli F, Manghisi OG, Correale M (2003) Are 90K/MAC-2BP serum levels correlated with poor prognosis in HCC patients? Preliminary results. Int J Biol Markers 18:222–226PubMed
22.
go back to reference Fornarini B, D’Ambrosio C, Natoli C, Tinari N, Silingardi V, Iacobelli S (2000) Adhesion to 90K (Mac-2 BP) as a mechanism for lymphoma drug resistance in vivo. Blood 96:3282–3285PubMed Fornarini B, D’Ambrosio C, Natoli C, Tinari N, Silingardi V, Iacobelli S (2000) Adhesion to 90K (Mac-2 BP) as a mechanism for lymphoma drug resistance in vivo. Blood 96:3282–3285PubMed
23.
go back to reference Zhang DS, Ding Y, Li YH, Xu RH, Wang B, Zhang XS et al (2005) Expression of glycoprotein 90K in non-Hodgkin’s lymphoma and its clinical significance. Ai Zheng 24:1006–1010PubMed Zhang DS, Ding Y, Li YH, Xu RH, Wang B, Zhang XS et al (2005) Expression of glycoprotein 90K in non-Hodgkin’s lymphoma and its clinical significance. Ai Zheng 24:1006–1010PubMed
24.
go back to reference Gentiloni N, Caradonna P, Costamagna G, D’Ostilio N, Perri V, Mutignani M et al (1995) Pancreatic juice 90K and serum CA 19-9 combined determination can discriminate between pancreatic cancer and chronic pancreatitis. Am J Gastroenterol 90:1069–1072PubMed Gentiloni N, Caradonna P, Costamagna G, D’Ostilio N, Perri V, Mutignani M et al (1995) Pancreatic juice 90K and serum CA 19-9 combined determination can discriminate between pancreatic cancer and chronic pancreatitis. Am J Gastroenterol 90:1069–1072PubMed
25.
go back to reference Jallal B, Powell J, Zachwieja J, Brakebusch C, Germain L, Jacobs J et al (1995) Suppression of tumor growth in vivo by local and systemic 90K level increase. Cancer Res 55:3223–3227PubMed Jallal B, Powell J, Zachwieja J, Brakebusch C, Germain L, Jacobs J et al (1995) Suppression of tumor growth in vivo by local and systemic 90K level increase. Cancer Res 55:3223–3227PubMed
26.
go back to reference Lahm H, Andre S, Hoeflich A, Kaltner H, Siebert HC, Sordat B et al (2004) Tumor galectinology: insights into the complex network of a family of endogenous lectins. Glycoconj J 20:227–238PubMedCrossRef Lahm H, Andre S, Hoeflich A, Kaltner H, Siebert HC, Sordat B et al (2004) Tumor galectinology: insights into the complex network of a family of endogenous lectins. Glycoconj J 20:227–238PubMedCrossRef
27.
go back to reference Becker R, Lenter MC, Vollkommer T, Boos AM, Pfaff D, Augustin HG et al (2008) Tumor stroma marker endosialin (Tem1) is a binding partner of metastasis-related protein Mac-2 BP/90K. FASEB J 22:3059–3067PubMedCrossRef Becker R, Lenter MC, Vollkommer T, Boos AM, Pfaff D, Augustin HG et al (2008) Tumor stroma marker endosialin (Tem1) is a binding partner of metastasis-related protein Mac-2 BP/90K. FASEB J 22:3059–3067PubMedCrossRef
28.
go back to reference Lee JH, Cho ES, Kim MY, Seo YW, Kho DH, Chung IJ et al (2005) Suppression of progression and metastasis of established colon tumors in mice by intravenous delivery of short interfering RNA targeting KITENIN, a metastasis-enhancing protein. Cancer Res 65:8993–9003PubMedCrossRef Lee JH, Cho ES, Kim MY, Seo YW, Kho DH, Chung IJ et al (2005) Suppression of progression and metastasis of established colon tumors in mice by intravenous delivery of short interfering RNA targeting KITENIN, a metastasis-enhancing protein. Cancer Res 65:8993–9003PubMedCrossRef
Metadata
Title
Prognostic relevance of LGALS3BP in human colorectal carcinoma
Authors
Enza Piccolo
Nicola Tinari
Domenica D’Addario
Cosmo Rossi
Valentina Iacobelli
Rossana La Sorda
Rossano Lattanzio
Maurizia D’Egidio
Annalisa Di Risio
Mauro Piantelli
Pier Giorgio Natali
Stefano Iacobelli
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0606-x

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