V3 versican isoform expression has a dual role in human melanoma tumor growth and metastasis.
Versican is a large chondroitin sulfate proteoglycan produced by several tumor cell types, including malignant melanoma, which exists as four different splice variants. The presence of versican in the extracellular matrix plays a role in tumor cell growth, adhesion and migration, which could be altered by altering the ratio between versican isoforms. We have previously shown that overexpression of the V3 isoform of versican in human melanoma cell lines markedly reduces cell growth in vitro and in vivo, since V3-overexpressing (LV3SN) cultured cells as well as primary tumors arising from these cells grow slower than their vector-only counterparts (LXSN). In the present work, we have extended these observations to demonstrate that the delayed cell growth is due to multiple events since differences in proliferative index as well as in apoptosis are observed in LV3SN cells and tumors compared to LXSN. For example, LV3SN melanoma cells exhibit delayed activation of MAPK in response to EGF, we have also characterized further the primary tumors originated in nude mice from V3-transduced melanoma cells to determine if other events affect the V3 tumor phenotype. For example, hyaluronan content of LV3SN tumors was higher than in LXSN tumors, whereas other related matrix components and vascularization were unaffected. Furthermore, lung metastasis in nude mice occurred only in animals carrying LV3SN tumors, indicating a dual role for this molecule, both as an inhibitor of tumor growth and a metastasis inductor.
Miquel-Serra
Laia
L
Facultat de Veterinària, Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, Bellaterra, Spain.
Serra
Montserrat
M
Hernández
Daniel
D
Domenzain
Clelia
C
Docampo
María José
MJ
Rabanal
Rosa M
RM
de Torres
Inés
I
Wight
Thomas N
TN
Fabra
Angels
A
Bassols
Anna
A
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D020033:Protein Isoforms; D011509:Proteoglycans; C508322:VCAN protein, human; D053675:Versicans