title: Epigenetic disruption of cadherin-11 in human cancer metastasis.
abstract: Little is known about the molecular events occurring in the metastases of human tumours. Epigenetic alterations are dynamic lesions that change over the natural course of the disease, and so they might play a role in the biology of cancer cells that have departed from the primary tumour. Herein, we have adopted an epigenomic approach to identify some of these changes. Using a DNA methylation microarray platform to compare paired primary tumour and lymph node metastatic cell lines from the same patient, we observed cadherin-11 promoter CpG island hypermethylation as a likely target of the process. We found that CDH11 DNA methylation-associated transcriptional silencing occurred in the corresponding lymph node metastases of melanoma and head and neck cancer cells but not in the primary tumours. Using in vitro and in vivo cellular and mouse models for depleted or enhanced CDH11 activity, we also demonstrated that CDH11 acts as an inhibitor of tumour growth, motility and dissemination. Most importantly, the study of CDH11 5'-CpG island hypermethylation in primary tumours and lymph node metastases of cancer patients showed this epigenetic alteration to be significantly confined to the disseminated cells. Overall, these results indicate the existence of metastasis-specific epigenetic events that might contribute to the progression of the disease.
authors.affiliation: Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Carmona
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.forename: Clara
authors.initials: C
authors.lastname: Muñoz
authors.forename: Sara
authors.initials: S
authors.lastname: Puertas
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Penin
authors.forename: Montserrat
authors.initials: M
authors.lastname: Gomà
authors.forename: Amaia
authors.initials: A
authors.lastname: Lujambio
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piulats
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesía
authors.forename: Montse
authors.initials: M
authors.lastname: Sánchez-Céspedes
authors.forename: Manel
authors.initials: M
authors.lastname: Manós
authors.forename: Enric
authors.initials: E
authors.lastname: Condom
authors.forename: Suzanne A
authors.initials: SA
authors.lastname: Eccles
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008817:Mice, Mutant Strains; D046228:Microarray Analysis; D009368:Neoplasm Transplantation / Q000379:methods; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; C086960:osteoblast cadherin