1. ¹Facultat de Veterinària, Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, Bellaterra, Spain
2. ²Facultat de Veterinària, Departament de Medicina i Cirurgia Animals, Universitat Autónoma de Barcelona, Bellaterra, Spain
3. ³Servei Anatomia Patológica, Hospital Vall d'Hebron, Barcelona, Spain
4. ⁴The Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA
5. ⁵Institut de Recerca Oncológica, L'Hospitalet de Llobregat, Spain

Correspondence: Dr A Bassols, PhD, Facultat de Veterinària, Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, 08193 Bellaterra, Spain. E-mail: anna.bassols@uab.es

Received 9 February 2006; Revised 31 May 2006; Accepted 3 June 2006; Published online 17 July 2006.

Abstract

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.