Skip to main content
Top
Published in: Archives of Dermatological Research 4/2014

01-05-2014 | Original Paper

miR-205 down-regulation promotes proliferation of dermatofibrosarcoma protuberans tumor cells by regulating LRP-1 and ERK phosphorylation

Authors: Ikko Kajihara, Masatoshi Jinnin, Miho Harada, Katsunari Makino, Noritoshi Honda, Takamitsu Makino, Toshikatsu Igata, Shinichi Masuguchi, Satoshi Fukushima, Hironobu Ihn

Published in: Archives of Dermatological Research | Issue 4/2014

Login to get access

Abstract

Dermatofibrosarcoma protuberans (DFSP) is an intermediate malignancy of the skin. Although COL1A1/PDGFB fusion gene was identified in the tumor cells recently, not all of the cases were positive for the fusion gene, and further researches are still needed to clarify the pathogenesis of DFSP. In this study, we investigated the role of microRNAs in the tumor. microRNA PCR array showed several microRNAs increased or decreased in DFSP in vivo compared with dermatofibroma (DF) and normal skin. Among them, the expression of miR-205 was down-regulated in DFSP compared with DF and normal skin. In situ hybridization showed that miR-205 expression was evident in dermal fibroblasts of normal skin although hardly detected in tumor cells of DF or DFSP. miR-205 inhibitor increased cell proliferation and the luciferase activity of 3′UTR of low-density lipoprotein receptor-related protein-1 (LRP-1) in cultured normal dermal fibroblasts. Immunohistochemistry showed the expression of LRP-1 was increased in DFSP tissue. Knockdown of LRP-1 suppressed cell growth and down-regulated extracellular signal-regulated kinase (ERK) phosphorylation without affecting MEK phosphorylation in cultured DFSP cells. Taken together, LRP-1 overexpression caused by the miR-205 down-regulation may play a role in the abnormal proliferation of DFSP cells via directly regulating ERK phosphorylation.
Literature
1.
go back to reference Allan AE, Tsou HC, Harrington A, Stasko T, Lee X, Si SP, Grande DJ, Peacocke M (1993) Clonal origin of dermatofibrosarcoma protuberans. J Invest Dermatol 100:99–102PubMedCrossRef Allan AE, Tsou HC, Harrington A, Stasko T, Lee X, Si SP, Grande DJ, Peacocke M (1993) Clonal origin of dermatofibrosarcoma protuberans. J Invest Dermatol 100:99–102PubMedCrossRef
3.
4.
go back to reference Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529PubMedCentralPubMedCrossRef Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529PubMedCentralPubMedCrossRef
5.
go back to reference Childs G, Fazzari M, Kung G, Kawachi N, Brandwein-Gensler M, McLemore M, Chen Q, Burk RD, Smith RV, Prystowsky MB, Belbin TJ, Schlecht NF (2009) Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol 174:736–745PubMedCentralPubMedCrossRef Childs G, Fazzari M, Kung G, Kawachi N, Brandwein-Gensler M, McLemore M, Chen Q, Burk RD, Smith RV, Prystowsky MB, Belbin TJ, Schlecht NF (2009) Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol 174:736–745PubMedCentralPubMedCrossRef
6.
go back to reference Dedieu S, Langlois B, Devy J, Sid B, Henriet P, Sartelet H, Bellon G, Emonard H, Martiny L (2008) LRP-1 silencing prevents malignant cell invasion despite increased pericellular proteolytic activities. Mol Cell Biol 28:2980–2995PubMedCentralPubMedCrossRef Dedieu S, Langlois B, Devy J, Sid B, Henriet P, Sartelet H, Bellon G, Emonard H, Martiny L (2008) LRP-1 silencing prevents malignant cell invasion despite increased pericellular proteolytic activities. Mol Cell Biol 28:2980–2995PubMedCentralPubMedCrossRef
7.
go back to reference Gandellini P, Folini M, Longoni N, Pennati M, Binda M, Colecchia M, Salvioni R, Supino R, Moretti R, Limonta P, Valdagni R, Daidone MG, Zaffaroni N (2009) miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon. Cancer Res 69:2287–2295PubMedCrossRef Gandellini P, Folini M, Longoni N, Pennati M, Binda M, Colecchia M, Salvioni R, Supino R, Moretti R, Limonta P, Valdagni R, Daidone MG, Zaffaroni N (2009) miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon. Cancer Res 69:2287–2295PubMedCrossRef
8.
go back to reference Geetha N, Mihaly J, Stockenhuber A, Blasi F, Uhrin P, Binder BR, Freissmuth M, Breuss JM (2011) Signal integration and coincidence detection in the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) cascade: concomitant activation of receptor tyrosine kinases and of LRP-1 leads to sustained ERK phosphorylation via down-regulation of dual specificity phosphatases (DUSP1 and -6). J Biol Chem 286:25663–25674PubMedCentralPubMedCrossRef Geetha N, Mihaly J, Stockenhuber A, Blasi F, Uhrin P, Binder BR, Freissmuth M, Breuss JM (2011) Signal integration and coincidence detection in the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) cascade: concomitant activation of receptor tyrosine kinases and of LRP-1 leads to sustained ERK phosphorylation via down-regulation of dual specificity phosphatases (DUSP1 and -6). J Biol Chem 286:25663–25674PubMedCentralPubMedCrossRef
9.
10.
go back to reference Greco A, Roccato E, Miranda C, Cleris L, Formelli F, Pierotti MA (2001) Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer 92:354–360PubMedCrossRef Greco A, Roccato E, Miranda C, Cleris L, Formelli F, Pierotti MA (2001) Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer 92:354–360PubMedCrossRef
11.
go back to reference Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34:D140–D144PubMedCentralPubMedCrossRef Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34:D140–D144PubMedCentralPubMedCrossRef
12.
go back to reference Honda N, Jinnin M, Kajihara I, Makino T, Makino K, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2012) TGF-beta-mediated downregulation of microRNA-196a contributes to the constitutive upregulated type I collagen expression in scleroderma dermal fibroblasts. J Immunol 188:3323–3331PubMedCrossRef Honda N, Jinnin M, Kajihara I, Makino T, Makino K, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2012) TGF-beta-mediated downregulation of microRNA-196a contributes to the constitutive upregulated type I collagen expression in scleroderma dermal fibroblasts. J Immunol 188:3323–3331PubMedCrossRef
13.
go back to reference Ihn H, Tamaki K (2002) Mitogenic activity of dermatofibrosarcoma protuberans is mediated via an extracellular signal related kinase dependent pathway. J Invest Dermatol 119:954–960PubMedCrossRef Ihn H, Tamaki K (2002) Mitogenic activity of dermatofibrosarcoma protuberans is mediated via an extracellular signal related kinase dependent pathway. J Invest Dermatol 119:954–960PubMedCrossRef
14.
go back to reference Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T, Menard S, Croce CM, Tagliabue E (2009) microRNA-205 regulates HER3 in human breast cancer. Cancer Res 69:2195–2200PubMedCrossRef Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T, Menard S, Croce CM, Tagliabue E (2009) microRNA-205 regulates HER3 in human breast cancer. Cancer Res 69:2195–2200PubMedCrossRef
15.
go back to reference Kajihara I, Jinnin M, Yamane K, Makino T, Honda N, Igata T, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2012) Increased accumulation of extracellular thrombospondin-2 due to low degradation activity stimulates type I collagen expression in scleroderma fibroblasts. Am J Pathol 180:703–714PubMedCrossRef Kajihara I, Jinnin M, Yamane K, Makino T, Honda N, Igata T, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H (2012) Increased accumulation of extracellular thrombospondin-2 due to low degradation activity stimulates type I collagen expression in scleroderma fibroblasts. Am J Pathol 180:703–714PubMedCrossRef
16.
go back to reference Kanemaru H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A, Masuguchi S, Ishihara T, Inoue Y, Jinnin M, Ihn H (2011) The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci 61:187–193PubMedCrossRef Kanemaru H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A, Masuguchi S, Ishihara T, Inoue Y, Jinnin M, Ihn H (2011) The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci 61:187–193PubMedCrossRef
17.
go back to reference Kerob D, Porcher R, Verola O, Dalle S, Maubec E, Aubin F, D’Incan M, Bodokh I, Boulinguez S, Madelaine-Chambrin I, Mathieu-Boue A, Servant JM, de Kerviler E, Janin A, Calvo F, Pedeutour F, Lebbe C (2010) Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patients. Clin Cancer Res 16:3288–3295PubMedCrossRef Kerob D, Porcher R, Verola O, Dalle S, Maubec E, Aubin F, D’Incan M, Bodokh I, Boulinguez S, Madelaine-Chambrin I, Mathieu-Boue A, Servant JM, de Kerviler E, Janin A, Calvo F, Pedeutour F, Lebbe C (2010) Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patients. Clin Cancer Res 16:3288–3295PubMedCrossRef
18.
go back to reference Kim HJ, Bar-Sagi D (2004) Modulation of signaling by Sprouty: developing story. Nat Rev Mol Cell Biol 5:441–450PubMedCrossRef Kim HJ, Bar-Sagi D (2004) Modulation of signaling by Sprouty: developing story. Nat Rev Mol Cell Biol 5:441–450PubMedCrossRef
19.
go back to reference Kohno M, Pouyssegur J (2006) Targeting the ERK signaling pathway in cancer therapy. Ann Med 38:200–211PubMedCrossRef Kohno M, Pouyssegur J (2006) Targeting the ERK signaling pathway in cancer therapy. Ann Med 38:200–211PubMedCrossRef
20.
go back to reference Lin N, Urabe K, Moroi Y, Uchi H, Nakahara T, Dainichi T, Kokuba H, Tu Y, Furue M (2006) Overexpression of phosphorylated-STAT3 and phosphorylated-ERK protein in dermatofibrosarcoma protuberans. Eur J Dermatol 16:262–265PubMed Lin N, Urabe K, Moroi Y, Uchi H, Nakahara T, Dainichi T, Kokuba H, Tu Y, Furue M (2006) Overexpression of phosphorylated-STAT3 and phosphorylated-ERK protein in dermatofibrosarcoma protuberans. Eur J Dermatol 16:262–265PubMed
21.
go back to reference Maekawa T, Jinnin M, Ihn H (2011) The expression levels of thrombospondin-1 in dermatofibroma and dermatofibrosarcoma protuberans. Eur J Dermatol 21:534–538PubMed Maekawa T, Jinnin M, Ihn H (2011) The expression levels of thrombospondin-1 in dermatofibroma and dermatofibrosarcoma protuberans. Eur J Dermatol 21:534–538PubMed
22.
go back to reference Makino K, Jinnin M, Aoi J, Hirano A, Kajihara I, Makino T, Sakai K, Fukushima S, Inoue Y, Ihn H (2013) Discoidin domain receptor 2-microRNA 196a-mediated negative feedback against excess type I collagen expression is impaired in scleroderma dermal fibroblasts. J Invest Dermatol 133:110–119PubMedCrossRef Makino K, Jinnin M, Aoi J, Hirano A, Kajihara I, Makino T, Sakai K, Fukushima S, Inoue Y, Ihn H (2013) Discoidin domain receptor 2-microRNA 196a-mediated negative feedback against excess type I collagen expression is impaired in scleroderma dermal fibroblasts. J Invest Dermatol 133:110–119PubMedCrossRef
23.
go back to reference Martin MM, Buckenberger JA, Jiang J, Malana GE, Nuovo GJ, Chotani M, Feldman DS, Schmittgen TD, Elton TS (2007) The human angiotensin II type 1 receptor +1166 A/C polymorphism attenuates microrna-155 binding. J Biol Chem 282:24262–24269PubMedCentralPubMedCrossRef Martin MM, Buckenberger JA, Jiang J, Malana GE, Nuovo GJ, Chotani M, Feldman DS, Schmittgen TD, Elton TS (2007) The human angiotensin II type 1 receptor +1166 A/C polymorphism attenuates microrna-155 binding. J Biol Chem 282:24262–24269PubMedCentralPubMedCrossRef
24.
go back to reference Muchemwa FC, Wakasugi S, Honda Y, Ihn H (2010) PDGFB quantification is a useful tool in the diagnosis of dermatofibrosarcoma protuberans: a study of 10 cases. Clin Exp Dermatol 35:295–299PubMedCrossRef Muchemwa FC, Wakasugi S, Honda Y, Ihn H (2010) PDGFB quantification is a useful tool in the diagnosis of dermatofibrosarcoma protuberans: a study of 10 cases. Clin Exp Dermatol 35:295–299PubMedCrossRef
25.
go back to reference Nuovo GJ (2008) In situ detection of precursor and mature microRNAs in paraffin embedded, formalin fixed tissues and cell preparations. Methods 44:39–46PubMedCrossRef Nuovo GJ (2008) In situ detection of precursor and mature microRNAs in paraffin embedded, formalin fixed tissues and cell preparations. Methods 44:39–46PubMedCrossRef
26.
go back to reference Pedeutour F, Turc-Carel C, Hecht BK, Hecht F (1995) Translocation basis for polychromosomal rings. Cancer Genet Cytogenet 85:157–158PubMedCrossRef Pedeutour F, Turc-Carel C, Hecht BK, Hecht F (1995) Translocation basis for polychromosomal rings. Cancer Genet Cytogenet 85:157–158PubMedCrossRef
27.
go back to reference Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM (2010) Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 28:1772–1779PubMedCentralPubMedCrossRef Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM (2010) Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 28:1772–1779PubMedCentralPubMedCrossRef
28.
go back to reference Shimizu A, O’Brien KP, Sjoblom T, Pietras K, Buchdunger E, Collins VP, Heldin CH, Dumanski JP, Ostman A (1999) The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 59:3719–3723PubMed Shimizu A, O’Brien KP, Sjoblom T, Pietras K, Buchdunger E, Collins VP, Heldin CH, Dumanski JP, Ostman A (1999) The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 59:3719–3723PubMed
29.
go back to reference Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C, O’Brien KP, Kedra D, Fransson I, Guilbaud C, Dumanski JP (1997) Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet 15:95–98PubMedCrossRef Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C, O’Brien KP, Kedra D, Fransson I, Guilbaud C, Dumanski JP (1997) Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet 15:95–98PubMedCrossRef
30.
go back to reference Sirvent N, Maire G, Pedeutour F (2003) Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer 37:1–19PubMedCrossRef Sirvent N, Maire G, Pedeutour F (2003) Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer 37:1–19PubMedCrossRef
31.
go back to reference Sjoblom T, Shimizu A, O’Brien KP, Pietras K, Dal Cin P, Buchdunger E, Dumanski JP, Ostman A, Heldin CH (2001) Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res 61:5778–5783PubMed Sjoblom T, Shimizu A, O’Brien KP, Pietras K, Dal Cin P, Buchdunger E, Dumanski JP, Ostman A, Heldin CH (2001) Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res 61:5778–5783PubMed
32.
go back to reference Song H, Bu G (2009) MicroRNA-205 inhibits tumor cell migration through down-regulating the expression of the LDL receptor-related protein 1. Biochem Biophys Res Commun 388:400–405PubMedCentralPubMedCrossRef Song H, Bu G (2009) MicroRNA-205 inhibits tumor cell migration through down-regulating the expression of the LDL receptor-related protein 1. Biochem Biophys Res Commun 388:400–405PubMedCentralPubMedCrossRef
33.
go back to reference Song H, Li Y, Lee J, Schwartz AL, Bu G (2009) Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res 69:879–886PubMedCentralPubMedCrossRef Song H, Li Y, Lee J, Schwartz AL, Bu G (2009) Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res 69:879–886PubMedCentralPubMedCrossRef
34.
go back to reference Su N, Qiu H, Chen Y, Yang T, Yan Q, Wan X (2013) miR-205 promotes tumor proliferation and invasion through targeting ESRRG in endometrial carcinoma. Oncol Rep 29:2297–2302PubMed Su N, Qiu H, Chen Y, Yang T, Yan Q, Wan X (2013) miR-205 promotes tumor proliferation and invasion through targeting ESRRG in endometrial carcinoma. Oncol Rep 29:2297–2302PubMed
35.
go back to reference Verdoodt B, Neid M, Vogt M, Kuhn V, Liffers ST, Palisaar RJ, Noldus J, Tannapfel A, Mirmohammadsadegh A (2013) MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer. Int J Oncol 43(1):307–314PubMed Verdoodt B, Neid M, Vogt M, Kuhn V, Liffers ST, Palisaar RJ, Noldus J, Tannapfel A, Mirmohammadsadegh A (2013) MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer. Int J Oncol 43(1):307–314PubMed
Metadata
Title
miR-205 down-regulation promotes proliferation of dermatofibrosarcoma protuberans tumor cells by regulating LRP-1 and ERK phosphorylation
Authors
Ikko Kajihara
Masatoshi Jinnin
Miho Harada
Katsunari Makino
Noritoshi Honda
Takamitsu Makino
Toshikatsu Igata
Shinichi Masuguchi
Satoshi Fukushima
Hironobu Ihn
Publication date
01-05-2014
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 4/2014
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-014-1452-z

Other articles of this Issue 4/2014

Archives of Dermatological Research 4/2014 Go to the issue