title: Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma.
abstract: Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels.
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Kawahara
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Granato
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Carnielli
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Nilva K
authors.initials: NK
authors.lastname: Cervigne
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Carine E
authors.initials: CE
authors.lastname: Oliveria
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: César
authors.initials: C
authors.lastname: Rivera
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: César A R
authors.initials: CA
authors.lastname: Martinez
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: Sami
authors.initials: S
authors.lastname: Yokoo
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Felipe P
authors.initials: FP
authors.lastname: Fonseca
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Marcio
authors.initials: M
authors.lastname: Lopes
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Santos-Silva
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Edgard
authors.initials: E
authors.lastname: Graner
authors.affiliation: Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, UNICAMP, Piracicaba, Brazil.
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas, Brazil.
authors.forename: Adriana Franco
authors.initials: AF
authors.lastname: Paes Leme
mesh_terms: D018171:Agrin / Q000235:genetics / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000503:physiopathology*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000503:physiopathology*
chemical_list: D018171:Agrin; D000970:Antineoplastic Agents; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan; D002945:Cisplatin