Artículo

Guttlein, L.N.; Benedetti, L.G.; Fresno, C.; Spallanzani, R.G.; Mansilla, S.F.; Rotondaro, C.; Iraolagoitia, X.L.R.; Salvatierra, E.; Bravo, A.I.; Fernandez, E.A.; Gottifredi, V.; Zwirner, N.W.; Llera, A.S.; Podhajcer, O.L. "Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC" (2017) Molecular Cancer Research. 15(3):304-316
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Understanding the mechanism of metastatic dissemination is crucial for the rational design of novel therapeutics. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein which has been extensively associated with human breast cancer aggressiveness although the underlying mechanisms are still unclear. Here, shRNA-mediated SPARC knockdown greatly reduced primary tumor growth and completely abolished lung colonization of murine 4T1 and LM3 breast malignant cells implanted in syngeneic BALB/c mice. A comprehensive study including global transcriptomic analysis followed by biological validations confirmed that SPARC induces primary tumor growth by enhancing cell cycle and by promoting a COX-2-mediated expansion of myeloid-derived suppressor cells (MDSC). The role of SPARC in metastasis involved a COX-2-independent enhancement of cell disengagement from the primary tumor and adherence to the lungs that fostered metastasis implantation. Interestingly, SPARC-driven gene expression signatures obtained from these murine models predicted the clinical outcome of patients with HER2-enriched breast cancer subtypes. In total, the results reveal that SPARC and its downstream effectors are attractive targets for antimetastatic therapies in breast cancer. Implications: These findings shed light on the prometastatic role of SPARC, a key protein expressed by breast cancer cells and surrounding stroma, with important consequences for disease outcome. © 2017 American Association for Cancer Research.

Registro:

Documento: Artículo
Título:Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC
Autor:Guttlein, L.N.; Benedetti, L.G.; Fresno, C.; Spallanzani, R.G.; Mansilla, S.F.; Rotondaro, C.; Iraolagoitia, X.L.R.; Salvatierra, E.; Bravo, A.I.; Fernandez, E.A.; Gottifredi, V.; Zwirner, N.W.; Llera, A.S.; Podhajcer, O.L.
Filiación:Laboratorio de Terapia Molecular y Celular, IIBBA, Fundacion Instituto Leloir, CONICET, Av. Patricias Argentinas 435, Buenos Aires, C1405BWE, Argentina
Unidad Asociada: Area de Cs. Agrarias Ingeniería, Cs. Biologicas y de la Salud. CONICET, Universidad Catolica de Cordoba, Cordoba, Argentina
Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina
Laboratorio de Ciclo Celular y Estabilidad Genomica, IIBBA, Fundacion Instituto Leloir, CONICET, Buenos Aires, Argentina
Unidad de Inmunopatología, Hospital Interzonal General de Agudos Eva Peron, Provincia de Buenos Aires, Argentina
Facultad de Ciencias Exactasy Naturales, Departamento de Química Biologica, Universidad de Buenos Aires, Buenos Aires, Argentina
Facultad de Ciencias Exactas Físicas y Naturales, Universidad Nacional de Cordoba, Cordoba, Argentina
Palabras clave:cyclooxygenase 2; epidermal growth factor receptor 2; osteonectin; short hairpin RNA; epidermal growth factor receptor 2; Erbb2 protein, mouse; osteonectin; SPARC protein, human; SPARC protein, mouse; animal cell; animal experiment; animal model; Article; breast cancer; cell expansion; clinical outcome; control; controlled study; female; gene expression; human; human tissue; major clinical study; metastasis; mouse; myeloid-derived suppressor cell; nonhuman; predictive value; primary tumor; priority journal; tumor growth; animal; Bagg albino mouse; breast tumor; cell growth; enzymology; experimental mammary neoplasm; genetics; MCF-7 cell line; metabolism; metastasis; pathology; physiology; prognosis; treatment outcome; tumor cell line; Animals; Breast Neoplasms; Cell Growth Processes; Cell Line, Tumor; Female; Humans; Mammary Neoplasms, Experimental; MCF-7 Cells; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Osteonectin; Prognosis; Receptor, ErbB-2; Treatment Outcome
Año:2017
Volumen:15
Número:3
Página de inicio:304
Página de fin:316
DOI: http://dx.doi.org/10.1158/1541-7786.MCR-16-0243-T
Título revista:Molecular Cancer Research
Título revista abreviado:Mol. Cancer Res.
ISSN:15417786
CODEN:MCROC
CAS:epidermal growth factor receptor 2, 137632-09-8; osteonectin, 104052-78-0; Erbb2 protein, mouse; Osteonectin; Receptor, ErbB-2; SPARC protein, human; SPARC protein, mouse
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15417786_v15_n3_p304_Guttlein

Referencias:

  • Howlader, N., Noone, A.M., Krapcho, M., Miller, D., Bishop, K., Altekruse, S.F., (2016) SEER Cancer Statistics Review, 1975-2013, , http://seer.cancer.gov/csr/1975_2013/, Bethesda, MD: National Cancer Institute
  • Ramaswamy, S., Ross, K.N., Lander, E.S., Golub, T.R., A molecular signature of metastasis in primary solid tumors (2003) Nat Genet, 33, pp. 49-54
  • Cummings, M.C., Simpson, P.T., Reid, L.E., Jayanthan, J., Skerman, J., Song, S., Metastatic progression of breast cancer: Insights from 50 years of autopsies (2014) J Pathol, 232, pp. 23-31
  • Minn, A.J., Gupta, G.P., Siegel, P.M., Bos, P.D., Shu, W., Giri, D.D., Genes that mediate breast cancer metastasis to lung (2005) Nature, 436, pp. 518-524
  • Watkins, G., Douglas-Jones, A., Bryce, R., Mansel, R.E., Jiang, W.G., Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes (2005) Prostaglandins Leukot Essent Fatty Acids, 72, pp. 267-272
  • Park, S.Y., Lee, H.E., Li, H., Shipitsin, M., Gelman, R., Polyak, K., Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer (2010) Clin Cancer Res, 16, pp. 876-887
  • Witkiewicz, A.K., Freydin, B., Chervoneva, I., Potoczek, M., Rizzo, W., Rui, H., Stromal CD10 and SPARC expression in ductal carcinoma in situ (DCIS) patients predicts disease recurrence (2010) Cancer Biol Ther, 10, pp. 391-396
  • Hsiao, Y.H., Lien, H.C., Hwa, H.L., Kuo, W.H., Chang, K.J., Hsieh, F.J., SPARC (osteonectin) in breast tumors of different histologic types and its role in the outcome of invasive ductal carcinoma (2010) Breast J, 16, pp. 305-308
  • Bergamaschi, A., Tagliabue, E., Sorlie, T., Naume, B., Triulzi, T., Orlandi, R., Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome (2008) J Pathol, 214, pp. 357-367
  • Eswaran, J., Cyanam, D., Mudvari, P., Reddy, S.D., Pakala, S.B., Nair, S.S., Transcriptomic landscape ofbreast cancers through mRNA sequencing (2012) Sci Rep, 2, p. 264
  • Azim, H.A., Jr., Singhal, S., Ignatiadis, M., Desmedt, C., Fumagalli, D., Veys, I., Association between SPARC mRNA expression, prognosis and response to neoadjuvant chemotherapy in early breast cancer: A pooled in-silico analysis (2013) PLoS One, 8, p. e62451
  • Helleman, J., Jansen, M.P., Ruigrok-Ritstier, K., Van Staveren, I.L., Look, M.P., Meijer-Van Gelder, M.E., Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response (2008) Clin Cancer Res, 14, pp. 5555-5564
  • Beck, A.H., Espinosa, I., Gilks, C.B., Van De Rijn, M., West, R.B., The fibromatosis signature defines a robust stromal response in breast carcinoma (2008) Lab Invest, 88, pp. 591-601
  • Ma, N., Gerhard, R., Fregnani, J.H., Nonogaki, S., Rierger, R.B., Netto, M.M., Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients (2011) Breast Cancer Res Treat, 126, pp. 1-14
  • Lien, H.C., Hsiao, Y.H., Lin, Y.S., Yao, Y.T., Juan, H.F., Kuo, W.H., Molecular signatures of metaplastic carcinoma of the breast by large-scale transcrip-tional profiling: Identification of genes potentially related to epithelial-mesenchymal transition (2007) Oncogene, 26, pp. 7859-7871
  • Briggs, J., Chamboredon, S., Castellazzi, M., Kerry, J.A., Bos, T.J., Transcriptional upregulation of SPARC, in response to c-Jun overexpression, contributes to increased motility and invasion of MCF7 breast cancer cells (2002) Oncogene, 21, pp. 7077-7091
  • Gilles, C., Bassuk, J.A., Pulyaeva, H., Sage, E.H., Foidart, J.M., Thompson, E.W., SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines (1998) Cancer Res, 58, pp. 5529-5536
  • Koblinski, J.E., Kaplan-Singer, B.R., VanOsdol, S.J., Wu, M., Engbring, J.A., Wang, S., Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis (2005) Cancer Res, 65, pp. 7370-7377
  • Ledda, M.F., Adris, S., Bravo, A.I., Kairiyama, C., Bover, L., Chernajovsky, Y., Suppression of SPARC expression by antisense RNA abrogates the tumor-igenicity of human melanoma cells (1997) Nat Med, 3, pp. 171-176
  • Alvarez, M.J., Prada, F., Salvatierra, E., Bravo, A.I., Lutzky, V.P., Carbone, C., Secreted protein acidic and richincysteine producedbyhuman melanoma cells modulates polymorphonuclear leukocyte recruitment and antitumor cytotoxic capacity (2005) Cancer Res, 65, pp. 5123-5132
  • Sangaletti, S., Stoppacciaro, A., Guiducci, C., Torrisi, M.R., Colombo, M.P., Leukocyte, rather than tumor-produced SPARC, determines stroma and collagen type IV deposition in mammary carcinoma (2003) J Exp Med, 198, pp. 1475-1485
  • Sangaletti, S., Di Carlo, E., Gariboldi, S., Miotti, S., Cappetti, B., Parenza, M., Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis (2008) Cancer Res, 68, pp. 9050-9059
  • Tang, J., Hu, M., Lee, S., Roblin, R., Primer mixture enhances PCR detection of Mycoplasma/Acholeplasma contaminants in cell cultures (1999) Vitro Cell Dev Biol Anim, 35, pp. 1-3
  • Carpenter, A.E., Jones, T.R., Lamprecht, M.R., Clarke, C., Kang, I.H., Friman, O., CellProfiler: Image analysis software for identifying and quantifying cell phenotypes (2006) Genome Biol, 7, p. R100
  • Schneider, C.A., Rasband, W.S., Eliceiri, K.W., NIH Image to ImageJ: 25 years of image analysis (2012) Nat Methods, 9, pp. 671-675
  • Adris, S., Chuluyan, E., Bravo, A., Berenstein, M., Klein, S., Jasnis, M., Mice vaccination with interleukin 12-transduced colon cancer cells potentiates rejection of syngeneic non-organ-related tumor cells (2000) Cancer Res, 60, pp. 6696-6703
  • Rubinstein, N., Alvarez, M., Zwirner, N.W., Toscano, M.A., Ilarregui, J.M., Bravo, A., Targeted inhibition ofgalectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege (2004) Cancer Cell, 5, pp. 241-251
  • Kanehisa, M., Goto, S., KEGG: Kyoto encyclopedia of genes and genomes (2000) Nucleic Acids Res, 28, pp. 27-30
  • Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium (2000) Nat Genet, 25, pp. 25-29
  • Ringner, M., Fredlund, E., Hakkinen, J., Borg, A., Staaf, J., GOBO: Geneexpression-based outcome for breast cancer online (2011) PLoS One, 6, p. e17911
  • Aslakson, C.J., Miller, F.R., Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor (1992) Cancer Res, 52, pp. 1399-1405
  • Urtreger, A., Ladeda, V., Puricelli, L., Rivelli, A., Vidal, M., Delustig, E., Modulation of fibronectin expression and proteolytic activity associated with the invasive and metastatic phenotype in two new murine mammary tumor cell lines (1997) Int J Oncol, 11, pp. 489-496
  • Chandra, D., Jahangir, A., Quispe-Tintaya, W., Einstein, M.H., Gravekamp, C., Myeloid-derived suppressor cells have a central role in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young and old mice (2013) Br J Cancer, 108, pp. 2281-2290
  • Spallanzani, R.G., Dalotto-Moreno, T., Raffo Iraolagoitia, X.L., Ziblat, A., Domaica, C.I., Avila, D.E., Expansion of CD11b()Ly6G ()Ly6C (int) cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions (2013) Cancer Immunol Immunother, 62, pp. 1781-1795
  • Sinha, P., Clements, V.K., Fulton, A.M., Ostrand-Rosenberg, S., Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells (2007) Cancer Res, 67, pp. 4507-4513
  • Podhajcer, O.L., Benedetti, L.G., Girotti, M.R., Prada, F., Salvatierra, E., Llera, A.S., The role ofthe matricellular proteinSPARC in the dynamic interaction between the tumor and the host (2008) Cancer Metastasis Rev, 27, pp. 691-705
  • Zardavas, D., Irrthum, A., Swanton, C., Piccart, M., Clinical management of breast cancer heterogeneity (2015) Nat Rev Clin Oncol, 12, pp. 381-394
  • Heselmeyer-Haddad, K., Berroa Garcia, L.Y., Bradley, A., Ortiz-Melendez, C., Lee, W.J., Christensen, R., Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression (2012) Am J Pathol, 181, pp. 1807-1822
  • Fenouille, N., Robert, G., Tichet, M., Puissant, A., Dufies, M., Rocchi, S., The p53/p21Cip1/Waf1 pathway mediates the effects of SPARC on melanoma cell cycle progression (2011) Pigment Cell Melanoma Res, 24, pp. 219-232
  • Fenouille, N., Puissant, A., Tichet, M., Zimniak, G., Abbe, P., Mallavialle, A., SPARC functions as an anti-stress factor by inactivating p53 through Akt-mediated MDM2 phosphorylation to promote melanoma cell survival (2011) Oncogene, 30, pp. 4887-4900
  • Ristimaki, A., Sivula, A., Lundin, J., Lundin, M., Salminen, T., Haglund, C., Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer (2002) Cancer Res, 62, pp. 632-635
  • Basu, G.D., Pathangey, L.B., Tinder, T.L., Lagioia, M., Gendler, S.J., Mukherjee, P., Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cellsinan in vivo model of spontaneous metastatic breast cancer (2004) Mol Cancer Res, 2, pp. 632-642
  • Gabrilovich, D.I., Ostrand-Rosenberg, S., Bronte, V., Coordinated regulation of myeloid cells by tumours (2012) Nat Rev Immunol, 12, pp. 253-268
  • Prada, F., Benedetti, L.G., Bravo, A.I., Alvarez, M.J., Carbone, C., Podhajcer, O.L., SPARC endogenous level, rather than fibroblast-produced SPARC or stro-ma reorganization induced by SPARC, is responsible for melanoma cell growth (2007) J Invest Dermatol, 127, pp. 2618-2628
  • Sangaletti, S., Tripodo, C., Santangelo, A., Castioni, N., Portararo, P., Gulino, A., Mesenchymal transition of high-grade breast carcinomas depends on extracellular matrix control of myeloid suppressor cell activity (2016) Cell Rep, 17, pp. 233-248
  • Dalotto-Moreno, T., Croci, D.O., Cerliani, J.P., Martinez-Allo, V.C., Dergan-Dylon, S., Mendez-Huergo, S.P., Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease (2013) Cancer Res, 73, pp. 1107-1117
  • Sangaletti, S., Tripodo, C., Sandri, S., Torselli, I., Vitali, C., Ratti, C., Osteopontin shapes immunosuppression in the metastatic niche (2014) Cancer Res, 74, pp. 4706-4719
  • Tichet, M., Prod'Homme, V., Fenouille, N., Ambrosetti, D., Mallavialle, A., Cerezo, M., Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis (2015) Nat Commun, 6, p. 6993
  • Staaf, J., Ringner, M., Vallon-Christersson, J., Jonsson, G., Bendahl, P.O., Holm, K., Identification of subtypes in human epidermal growth factor receptor 2-positive breast cancer reveals a gene signature prognostic of outcome (2010) J Clin Oncol, 28, pp. 1813-1820
  • Desmedt, C., Haibe-Kains, B., Wirapati, P., Buyse, M., Larsimont, D., Bon-Tempi, G., Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes (2008) Clin Cancer Res, 14, pp. 5158-5165
  • Alexe, G., Dalgin, G.S., Scanfeld, D., Tamayo, P., Mesirov, J.P., DeLisi, C., High expression of lymphocyte-associated genes in node-negative HER2 breast cancers correlates with lower recurrence rates (2007) Cancer Res, 67, pp. 10669-10676

Citas:

---------- APA ----------
Guttlein, L.N., Benedetti, L.G., Fresno, C., Spallanzani, R.G., Mansilla, S.F., Rotondaro, C., Iraolagoitia, X.L.R.,..., Podhajcer, O.L. (2017) . Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC. Molecular Cancer Research, 15(3), 304-316.
http://dx.doi.org/10.1158/1541-7786.MCR-16-0243-T
---------- CHICAGO ----------
Guttlein, L.N., Benedetti, L.G., Fresno, C., Spallanzani, R.G., Mansilla, S.F., Rotondaro, C., et al. "Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC" . Molecular Cancer Research 15, no. 3 (2017) : 304-316.
http://dx.doi.org/10.1158/1541-7786.MCR-16-0243-T
---------- MLA ----------
Guttlein, L.N., Benedetti, L.G., Fresno, C., Spallanzani, R.G., Mansilla, S.F., Rotondaro, C., et al. "Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC" . Molecular Cancer Research, vol. 15, no. 3, 2017, pp. 304-316.
http://dx.doi.org/10.1158/1541-7786.MCR-16-0243-T
---------- VANCOUVER ----------
Guttlein, L.N., Benedetti, L.G., Fresno, C., Spallanzani, R.G., Mansilla, S.F., Rotondaro, C., et al. Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC. Mol. Cancer Res. 2017;15(3):304-316.
http://dx.doi.org/10.1158/1541-7786.MCR-16-0243-T