[en] BACKGROUND: Bone is a preferred target for circulating metastatic breast cancer cells. We found that the CD9 protein was up-regulated in the B02 osteotropic cell line, derived from the aggressive parental MDA-MB-231 breast cancer cell line. Here, we investigated the putative relationship between CD9 expression and the osteotropic phenotype. MATERIALS AND METHODS: Overexpression of CD9 was analyzed by immunoblotting in different cell lines. Immunohistochemistry was used to assess CD9 expression in primary tumors and metastatic lesions. In vivo experiments were conducted in mice using a monoclonal antibody against CD9. RESULTS: CD9 overexpression was confirmed in osteotropic cells. CD9 was significantly overexpressed in bone metastases versus primary tumors and visceral metastatic lesions. Finally, in vivo experiments showed that an antibody against CD9 delays homing of B02 cells in bone marrow, slowing down bone destruction. CONCLUSION: Our study reveals a potential implication of CD9 in the formation of bony metastases from breast cancer cells.
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Deux, Blandine
Lamour, Virginie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Dobson, Rowan
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)
Clezardin, Philippe
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
Overexpression of CD9 in human breast cancer cells promotes the development of bone metastases.
Publication date :
2012
Journal title :
Anticancer Research
ISSN :
0250-7005
eISSN :
1791-7530
Publisher :
International Institute of Anticancer Research, Greece
Volume :
32
Issue :
12
Pages :
5211-20
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 201342 - ADAMANT - ANTIBODY DERIVATIVES AS MOLECULAR AGENTS FOR NEOPLASTIC TARGETING
Funders :
EU FP6 STROMA EU FP7 ADAMANT F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Fondation Léon Fredericq [BE] CE - Commission Européenne [BE]
Coleman RE and Rubens RD: The clinical course of bone metastases from breast cancer. Br J Cancer 55: 61-66, 1987.
Galasko CS: Skeletal metastases. Clin Orthop Relat Res pp. 18-30, 1986.
Coleman RE: Skeletal complications of malignancy. Cancer 80: 1588-1594, 1997.
Kischel P, Guillonneau F, Dumont B, Bellahcene A, Stresing V, Clezardin P, De Pauw EA and Castronovo V: Cell membrane proteomic analysis identifies proteins differentially expressed in osteotropic human breast cancer cells. Neoplasia 10: 1014- 1020, 2008.
Berditchevski F: Complexes of tetraspanins with integrins: More than meets the eye. J Cell Sci 114: 4143-4151, 2001.
Levy S and Shoham T: Protein-protein interactions in the tetraspanin web. Physiology 20: 218-224, 2005.
Ikeyama S, Koyama M, Yamaoko M, Sasada R and Miyake M: Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA. J Exp Med 177: 1231-1237, 1993.
Ishii M, Iwai K, Koike M, Ohshima S, Kudo-Tanaka E, Ishii T, Mima T, Katada Y, Miyatake K, Uchiyama Y and Saeki Y: RANKL-induced expression of tetraspanin CD9 in lipid raft membrane microdomain is essential for cell fusion during osteoclastogenesis. J Bone Miner Res 21: 965-976, 2006.
Huang CI, Kohno N, Ogawa E, Adachi M, Taki T and Miyake M: Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. Am J Pathol 153: 973-983, 1998.
Miyake M, Nakano K, Itoi SI, Koh T and Taki T: Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer. Cancer Res 56: 1244-1249, 1996.
Adachi M, Taki T, Ieki Y, Huang CL, Higashiyama M and Miyake M: Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer. Cancer Res 56: 1751-1755, 1996.
Higashiyama M, Doi O, Kodama K, Yokouchi H, Adachi M, Huang CL, Taki T, Kasugai T, Ishiguro S, Nakamori S and Miyake M: Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis. Int J Cancer 74: 205-211, 1997.
Miyamoto S, Maruyama A, Okugawa K, Akazawa K, Baba H, Maehara Y and Mekada E: Loss of motility-related protein 1 (MRP1/CD9) and integrin α3 expression in endometrial cancers. Cancer 92: 542-548, 2001.
Sho M, Adachi M, Taki T, Hashida H, Konishi T, Huang CL, Ikeda N, Nakajima Y, Kanehiro H, Hisanaga M, Nakano H and Miyake M: Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer. Int J Cancer 79: 509-516, 1998.
Hashida H, Takabayashi A, Tokuhara T, Taki T, Kondo K, Kohno N, Yamaoka Y and Miyake M: Integrin alpha3 expression as a prognostic factor in colon cancer: Association with MRP-1/CD9 and KAI1/CD82. Int J Cancer 97: 518-525, 2002.
Erovic BM, Pammer J, Hollemann D, Woegerbauer M, Geleff S, Fischer MB, Burian M, Frommlet F and Neuchrist C: Motility-related protein-1/CD9 expression in head and neck squamous cell carcinoma. Head Neck 25: 848-857, 2003.
Yau JC, Dabbagh LK, Formenti KS, Coupland RW, Burns BF and Shaw AR: Expression of transmembrane 4 superfamily member, CD9, is related to improved progression-free survival in patients with diffuse non-Hodgkin's lymphoma. Oncol Rep 5: 1507-1511, 1998.
Si Z and Hersey P: Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma. Int J Cancer 54: 37-43, 1993.
Uchida S, Shimada Y, Watanabe G, Li ZG, Hong T, Miyake M and Imamura M: Motility-related protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer 79: 1168-1173, 1999.
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA and Massague J: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3: 537-549, 2003.
Yoneda T, Williams PJ, Hiraga T, Niewolna M and Nishimura R: A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro. J Bone Miner Res 16: 1486-1495, 2001.
Peyruchaud O, Winding B, Pecheur I, Serre CM, Delmas P and Clezardin P: Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: Application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions. J Bone Miner Res 16: 2027-2034, 2001.
Pecheur I, Peyruchaud O, Serre CM, Guglielmi J, Voland C, Bourre F, Margue C, Cohen-Solal M, Buffet A, Kieffer N and Clezardin P: Integrin αvβ3 expression confers on tumor cells a greater propensity to metastasize to bone. FASEB J 16: 1266-1268, 2002.
Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, von Eschenbach AC and Chung LW: Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54: 2577-2581, 1994.
Lin DL, Tarnowski CP, Zhang J, Dai J, Rohn E, Patel AH, Morris MD and Keller ET: Bone metastatic LNCaP-derivative C4-2B prostate cancer cell line mineralizes in vitro. Prostate 47: 212-221, 2001.
Waltregny D, Bellahcene A, Van Riet I, Fisher LW, Young M, Fernandez P, Dewe W, de Leval J and Castronovo V: Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer. J Natl Cancer Inst 90: 1000-1008, 1998.
Daubiné F, Le Gall C, Gasser J, Green J and Clézardin P: Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. J Natl Cancer Inst 99: 322-330, 2007.
Auerbach R, Lu WC, Pardon E, Gumkowski F, Kaminska G and Kaminski M: Specificity of adhesion between murine tumor cells and capillary endothelium: An in vitro correlate of preferential metastasis in vivo. Cancer Res 47: 1492-1496, 1987.
Ruoslahti E and Rajotte D: An address system in the vasculature of normal tissues and tumors. Annu Rev Immunol 18: 813-827, 2000.
Chambers AF, Groom AC and MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2: 563-572, 2002.
Hopkins AL and Groom CR: The druggable genome. Nat Rev Drug Discov 1: 727-730, 2002.
Bellahcene A, Bachelier R, Detry C, Lidereau R, Clezardin P and Castronovo V: Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells. Breast Cancer Res Treat 101: 135-148, 2007.
Gronborg M, Kristiansen TZ, Iwahori A, Chang R, Reddy R, Sato N, Molina H, Jensen ON, Hruban RH, Goggins MG, Maitra A and Pandey A: Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics 5: 157-171, 2006.
Jamil F, Peston D and Shousha S: CD9 immunohistochemical staining of breast carcinoma: Unlikely to provide useful prognostic information for routine use. Histopathology 39: 572-577, 2001.
Kubista B, Erovic BM, Klinger H, Sulzbacher I and Trieb K: CD9 expression is not a prognostic factor in human osteosarcoma. Cancer Lett 209: 105-110, 2004.
Longo N, Yanez-Mo M, Mittelbrunn M, de la Rosa G, Munoz ML, Sanchez-Madrid F and Sanchez-Mateos P: Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells. Blood 98: 3717-3726, 2001.
Sauer G, Windisch J, Kurzeder C, Heilmann V, Kreienberg R and Deissler H: Progression of cervical carcinomas is associated with down-regulation of CD9 but strong local re-expression at sites of transendothelial invasion. Clin Cancer Res 9: 6426-6431, 2003.
Leung KT, Chan KYY, Ng PC, Lau TK, Chiu WM, Tsang KS, Li CK, Kong CKL and Li K: The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells. Blood 117: 1840-1850, 2011.
De Bruyne E, Andersen TL, De Raeve H, Van Valckenborgh E, Caers J, Van Camp B, Delaisse JM, Van Riet I and Vanderkerken K: Endothelial cell-driven regulation of CD9 or motility-related protein-1 expression in multiple myeloma cells within the murine 5T33MM model and myeloma patients. Leukemia 20: 1870-1879, 2006.
Hori H, Yano S, Koufuji K, Takeda J and Shirouzu K: CD9 expression in gastric cancer and its significance. J Surg Res 117: 208-215, 2004.
Zoller M: Tetraspanins: Push and pull in suppressing and promoting metastasis. Nat Rev Cancer 9: 40-55, 2009.
Sloan EK, Pouliot N, Stanley KL, Chia J, Moseley JM, Hards DK and Anderson RL: Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone. Breast Cancer Res 8: R20, 2006.
Zhao Y, Bachelier R, Treilleux I, Pujuguet P, Peyruchaud O, Baron R, Clement-Lacroix P and Clezardin P: Tumor αvβ3 integrin is a therapeutic target for breast cancer bone metastases. Cancer Res 67: 5821-5830, 2007.