Melanocyte transformation associated with substrate adhesion impediment.
Exclude experimental models of malignant transformation employ chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a) to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for beta1 chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyltransferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.
Oba-Shinjo
Sueli M
SM
Laboratório de Biologia Molecular, Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Correa
Mariangela
M
Ricca
Tatiana I
TI
Molognoni
Fernanda
F
Pinhal
Maria A
MA
Neves
Izabel A
IA
Marie
Sueli K
SK
Sampaio
Lúcia O
LO
Nader
Helena B
HB
Chammas
Roger
R
Jasiulionis
Miriam G
MG
D000818:Animals; D023102:Anoikis; D002448:Cell Adhesion; D002461:Cell Line, Transformed / Q000637:transplantation; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured / Q000166:cytology; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D016895:Culture Media, Serum-Free; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005353:Fibronectins; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics; D006025:Glycosaminoglycans / Q000032:analysis; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D016023:Integrins / Q000378:metabolism; D007797:Laminin; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053675:Versicans; D000099175:Heparanase
D011508:Chondroitin Sulfate Proteoglycans; D016895:Culture Media, Serum-Free; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005966:Glucuronidase; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D016023:Integrins; D007797:Laminin; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012334:RNA, Neoplasm; D053675:Versicans; D000099175:Heparanase; C546879:Dcn protein, mouse; C508323:Vcan protein, mouse; C071927:perlecan